Rise In Arterial Blood Pressure Research Articles

The Arterial Baroreflex Buffers Muscle Metaboreflex-Induced Coronary Vasoconstriction

The ability to increase cardiac output and thereby skeletal muscle blood flow during dynamic exercise is paramount to maintaining exercise workload. Increases in cardiac output are driven via increases in heart rate, ventricular function, and central blood volume mobilization which raises arterial blood pressure, in part, due to activation of the muscle metaboreflex. The increase in cardiac sympathetic tone also activates coronary vascular alpha-adrenergic receptors which restrains increases in coronary blood flow which limits increases in ventricular function. During submaximal dynamic exercise, the muscle metaboreflex acts primarily to raise cardiac output with little net peripheral vasoconstriction. However, after sinoaortic baroreceptor denervation (SAD), the muscle metaboreflex causes increases in both cardiac output and total peripheral resistance indicating that the baroreflex buffers the muscle metaboreflex mainly via restraint of peripheral vasoconstriction. To what degree the arterial baroreflex restrains muscle metaboreflex-induced coronary vasoconstriction is unknown. Therefore, we utilized our chronically instrumented canine model to evaluate if SAD would significantly impact muscle metaboreflex-induced coronary vasoconstriction. Canines were chronically instrumented to measure cardiac output, left circumflex coronary artery blood flow, hindlimb blood flow and arterial blood pressure. During steady-state mild treadmill exercise (3.2 kph, 0% grade) the muscle metaboreflex was activated via partial inflation of vascular occluders placed distal to the hindlimb blood flow probe. Metaboreflex activation caused substantial increases in cardiac output, heart rate, cardiac power, coronary blood flow, and arterial blood pressure. Assessment of coronary vasodilation was performed via linear regression of the relationship between coronary vascular conductance (CVC; coronary blood flow/mean arterial pressure) vs. cardiac power (CP, an index of O2 demand). Experiments were performed at least 2 weeks after chronic bilateral SAD. Muscle metaboreflex activation after SAD caused a significantly greater pressor response driven by increases in both cardiac output and total peripheral resistance. Furthermore, after SAD the slope of the CVC-CP relationship was significantly lower during muscle metaboreflex activation (0.072 ml/min/mmHg/Watt, control vs 0.033 ml/min/mmHg/Watt, SAD; p<0.05) We conclude that the arterial baroreflex buffers the muscle metaboreflex and restrains the reflex coronary vasoconstriction. This baroreflex-induced restraint of metaboreflex mediated coronary vasoconstriction potentially limits metaboreflex-induced reductions myocardial oxygen delivery. Augmented coronary vasoconstriction with metaboreflex activation after SAD likely contributes to the smaller role of cardiac output in mediating the rise in arterial blood pressure after SAD, and provides further evidence that baroreflex buffering of metaboreflex responses improves cardiac function. Thus, reduced baroreflex function in heart failure may contribute to the accentuated metaboreflex coronary vasoconstriction which impairs ventricular performance during exercise in heart failure. This work was supported by the National Heart, Lung and, Blood Institute grants HL-055473, HL-126706. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The potential of methylene blue in treating septic shock: Is it worth a shot?

Shock is a circulatory failure that results in insufficient oxygen supply to cells. Septic shock is the most common variety in patients admitted to the Intensive Care Unit (ICU) and is a fatal condition that accounts for a considerable number of deaths in the ICU. [1, 2]. Treatment of septic shock consists of a triad that comprises hemodynamic resuscitation via crystalloid, vasopressor infusion and antibiotic delivery within the first hour of recognition [2]. Despite the evidence that these measures help reduce mortality, the percentage of death remains greater than 40%, necessitating the requirement for alternative treatment strategies [2]. Research shows that methylene blue significantly increases mean arterial pressure (MAP) and systemic vascular resistance (SVR).Furthermore, treatment with methylene blue aids in the tapering of vasopressors [3]. In a recent single-centre randomised control trial including patients suffering from septic shock, Ibarra-Estrada et al. Investigated the effect of early adjuvant methylene blue on time to vasopressor discontinuation. They discovered that in comparison to the control group, patients who were administered methylene blue had decreased time to vasopressor discontinuation with no adverse but rather had a shorter length of ICU and hospital stay [4]. Another trial by R. Ismail et al. involving preterm neonates with refractory septic shock reported similar findings where methylene blue led to a significant rise in arterial blood pressure, reducing the need for norepinephrine [5]. In addition, pooled data from a systematic review and meta-analysis shows that the use of MB in conjunction with vasopressors dramatically reduced mortality in patients with vasodilatory shock. These findings suggest that methylene blue has favourable outcomes in treating septic shock. Due to limited data, more research is required to compare the efficacy of methylene blue in different types of shock states and in different subgroups such as neonates, adolescents, adults and the elderly population. At this stage, more evidence regarding the short-term and long-term benefits and possible side effects of using methylene blue is also required, to allow physicians to be able to incorporate it in regular treatment protocols when practicing evidence-based medicine. Newer studies could help shed some light on appropriate dosing regimens and discover populations that would reap the most benefits from its use. Accurate conclusions, drawn via systematic reviews and meta-analyses including newer large-scale multi-centred clinical trials might be just what is needed to enhance the already existing treatment regimens for shock.

Cardiovascular responses to static handgrip exercise and postexercise ischemia in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by reduced ability to sustain physical activity that may be due partly to disease-related changes in autonomic function that contribute to dysregulated cardiovascular control during muscular contraction. Thus, we used a combination of static handgrip exercise (HG) and postexercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in 16 patients with HFpEF and 17 healthy, similarly aged controls. Changes in MAP were lower in patients with HFpEF compared with controls during both 30%MVC (Δ11 ± 7 vs. Δ15 ± 8 mmHg) and 40%MVC (Δ19 ± 14 vs. Δ30 ± 8 mmHg), and a similar pattern of response was evident during PEI (30%MVC: Δ8 ± 5 vs. Δ12 ± 8 mmHg; 40%MVC: Δ13 ± 10 vs. Δ18 ± 9 mmHg) (group effect: P = 0.078 and P = 0.017 at 30% and 40% MVC, respectively). Changes in HR, CO, and TPR did not differ between groups during HG or PEI (P > 0.05). Taken together, these data suggest a reduced pressor response to static muscle contractions in patients with HFpEF compared with similarly aged controls that may be mediated partly by a blunted muscle metaboreflex. These findings support a disease-related dysregulation in neural cardiovascular control that may reduce an ability to sustain physical activity in HFpEF.NEW & NOTEWORTHY The current investigation has identified a diminution in the exercise-induced rise in arterial blood pressure (BP) that persisted during postexercise ischemia (PEI) in an intensity-dependent manner in patients with heart failure with preserved ejection fraction (HFpEF) compared with older, healthy controls. These findings suggest that the pressor response to exercise is reduced in patients with HFpEF, and this deficit may be mediated, in part, by a blunted muscle metaboreflex, highlighting the consequences of impaired neural cardiovascular control during exercise in this patient group.

Clinico-epidemiological profile and risk factors of hypertensive crisis among patients attended at a tertiary care hospital in Somalia

Hypertensive crisis (HC) is a life-threatening clinical condition in which an abrupt rise in arterial blood pressure can lead to acute damage to vital organs. The main objective of our study is to determine the epidemiological profile, clinical characteristics, and risk factors of hypertensive crisis patients in Somalia. This study was a prospective cross-sectional study conducted on HC patients attended at Mogadishu Somali Turkish Training and Research Hospital in Mogadishu, Somalia, from November 2020 to April 2021. A total of 6239 patients were screened during the study period. The prevalence of HC was 2.1% (128/6239). Of them, 76 (59.4%) were males. The mean (SD) age of the participants was 56.5 (± 16.9) years (range: 24–98 years). 54.7% (70/128) met the criteria for a hypertensive emergency, while 45.3% (58/128) met the criteria of hypertensive urgency. Most patients (55.5%) took a single antihypertensive medicine, with calcium channel blockers being the most frequently used (57.8%). Headache and palpitation were the most often reported symptoms upon admission (39.1% and 25%). The most often prescribed antihypertensive drugs for the initial therapy included Intravenous furosemide (35.2%), Sublingual captopril (25.8%), intravenous nitroglycerin (23.4%), and intravenous labetalol (20%). Among the forms or patterns of end-organ damage of HE, we most frequently observed acute heart failure (45.7%), acute pulmonary edema (29.9%), and acute renal injury (25.7%). Infrequent medical checkups, poor compliance with medications, poor compliance with exercise, positive family history of hypertension, and being male gender were significant predictors of HC, AOR = 20.312; p < 0.000, AOR = 7.021; p < 0.008, AOR = 6.158; p < 0.017, AOR = 3.545; p < 0.032, and AOR = 2.144; p = 0.001, respectively. In Somalia, the hypertensive crisis is common in this clinic population. Infrequent medical checkups, poor compliance with medications and exercise, positive family history of hypertension, and being male gender were significant predictors of HC.

Latent Hypertension and Dysautonomia Among Athletes With Office Prehypertension During One Year Training Macrocycle

The research topicality is needed to diagnose in time and correct properly athletes’ autonomic dysfunction (especially among sportspeople with pre-pathological states). The study of latent hemodynamic changes and detection of dysautonomia among prehypertension athletes (particularly those who train heavily) is a promising way to raise sportsmen’s health and achievements. The research purpose is a hemodynamic profile study of athletes with office prehypertension during different training macrocycle periods. Methods. The research comprised 30 athletes of acyclic activity. Their average age was 23.1 (2.71) years. Females were nine individuals (30%). We monitored arterial blood pressure and heart rate in each macrocycle period, carried out the dysautonomia test and established anamnesis and complaints. Results. For prehypertension athletes, the most challenging moment was the competition period. Therefore, the systolic arterial hypertension rate within preparation, competitive and transition training periods was 17%, 47% and 7% (χ2=14.53; р0.001) while the diastolic one was 17%, 37% and 7% respectively (χ2=8.75; р=0.012). Significantly, we observed an increasing possibility of arterial blood pressure rise over normal values among dysautonomia athletes during the competition period (RR=3.27 (р=0.01); OR=8.33 (р=0.006)). However, during the preparation and recovery periods, arterial hypertension possibility was not significant (р0.05). Conclusions. In the competition period of training macrocycle is highly expectable development of arterial hypertension of latent course in athletes with office prehypertension. Besides, the relative risk of latent arterial hypertension in extra-training time increases if there are other symptoms of dysautonomia, but these changes are not persistent. However, their proper diagnosing and correcting may lead to athletes’ better health and achievements.

PD56-04 ASSESSMENT OF CHANGES IN ARTERIAL BLOOD PRESSURE AFTER NEPHRECTOMY FOR KIDNEY CANCER VAPANCR (UROCCR 26)_PROSPECTIVE STUDY

You have accessJournal of UrologyCME1 May 2022PD56-04 ASSESSMENT OF CHANGES IN ARTERIAL BLOOD PRESSURE AFTER NEPHRECTOMY FOR KIDNEY CANCER VAPANCR (UROCCR 26)_PROSPECTIVE STUDY Pierre Bigot, Jean-Christophe Bernhard, Nicolas Doumerc, François-Xavier Nouhaud, Idir Ouzaid, Patrick Saulnier, Arnaud Mejean, Morgan Rouprêt, and Karim Bensalah Pierre BigotPierre Bigot More articles by this author , Jean-Christophe BernhardJean-Christophe Bernhard More articles by this author , Nicolas DoumercNicolas Doumerc More articles by this author , François-Xavier NouhaudFrançois-Xavier Nouhaud More articles by this author , Idir OuzaidIdir Ouzaid More articles by this author , Patrick SaulnierPatrick Saulnier More articles by this author , Arnaud MejeanArnaud Mejean More articles by this author , Morgan RouprêtMorgan Rouprêt More articles by this author , and Karim BensalahKarim Bensalah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002636.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney is an essential regulator of arterial blood pressure (ABP) via the renin-angiotensin system. The impact of kidney surgery on ABP is debated. Our objective was to evaluate the consequences of kidney surgery for cancer on ABP. METHODS: We carried out a multicenter prospective study (NCT03218319) and included 200 patients who underwent nephrectomy for cancer between January 2018 and September 2020 at 7 academic centers from the UROCCR network. The study obtained approval from Ethical Committee (2017-A00127-46). Inclusions criteria were a localized cancer eligible to nephrectomy and the absence of pre-existing hypertension. ABP was monitored according to the recommendations for home blood pressure measurement. Four measurements were taken after 5 minutes of sitting rest, before breakfast and four additional measurements were taken in the evening before bedtime. Measurements were done during three consecutive days (average of 18 values). ABP evaluation was done the week before nephrectomy, one month and six months after nephrectomy. A renin assessment was done one week before surgery and 6 months after surgery. The primary endpoint was the occurrence of a clinically significant change in ABP at 6 months. A change in ABP was considered clinically significant if the variation in systolic and / or diastolic ABP was ≥ 5 mmHg or if medical anti-hypertensive treatment was required. RESULTS: ABP and renin measurements were evaluable for 182 (91%) and 136 (68%) patients, respectively. There were 112 males and 88 females with a median age of 54 years. Radical (RN) and Partial nephrectomy (PN) were performed in 42 (21%) and 158 (79%) patients, respectively. At 6 months, 55 (30.2%) patients had a significant increase in their ABP and 12 (6.5%) patients started an antihypertensive treatment. Type of surgery was not associated with increases in ABP (31.6 % PN vs 25% RN; p=0.559) nor prescription of antihypertensive drug (4.79% PN vs 12.5 % RN; p=0.089). At 6 months, renin was not significantly higher than before surgery (16.098 vs 15.231, p=0.686). In multivariable analysis, type of surgery, age, sex, BMI, smoking, diabetes and dyslipidemia were not associated with significant changes in ABP. CONCLUSIONS: Renal surgery for cancer induces significant variations in ABP in 30% of patients. Type of surgery is not associated with ABP outcomes. ABP after surgery seems not be related to renin secretion. Longer follow-up and additional patients will be necessary to determine whether this rise in ABP can have a consequence on the occurrence of cardio-vascular events. Source of Funding: This study was granted by the French Association of Urology (AFU) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e954 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pierre Bigot More articles by this author Jean-Christophe Bernhard More articles by this author Nicolas Doumerc More articles by this author François-Xavier Nouhaud More articles by this author Idir Ouzaid More articles by this author Patrick Saulnier More articles by this author Arnaud Mejean More articles by this author Morgan Rouprêt More articles by this author Karim Bensalah More articles by this author Expand All Advertisement PDF DownloadLoading ...

Aversive emotion rapidly activates orexin neurons and increases heart rate in freely moving mice

The perifornical area of the hypothalamus has been known as the center for the defense response, or fight-or-flight response, which is characterized by a concomitant rise in arterial blood pressure, heart rate, and respiratory frequency. It is well established that orexin neurons, which are located in this region, play a critical role in this response. In this study, we further examined this role by recording orexin neuronal activity and heart rate in freely moving mice using an original dual-channel fiber photometry system in vivo. Analysis of orexin neuron activity in relation to autonomic responses to aversive stimuli revealed a rapid increase in neuronal activity just prior to changes in heart rate. In addition, we examined whether orexin neurons would be activated by a conditioned neutral sound that was previously associated with aversive stimulus. We show that the memory of the aversive stimulus activated orexin neurons and increased heart rate. Our data suggest that orexin neurons are a key component linking aversive emotions to autonomic defense response. Our data also suggest that targeting orexin neurons may enable treatment of psychiatric disorders associated with chronic stress and traumatic memories.

Spectral Cerebral Blood Volume Accounting for Noninvasive Estimation of Changes in Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

We present the application of a new method for non-invasive cerebral perfusion pressure estimation (spectral nCPP or nCPPs) accounting for changes in transcranial Doppler-derived pulsatile cerebral blood volume. Primarily, we analysed cases in which CPP was changing (delta [∆],magnitude of changes]): (1) rise during vasopressor-induced augmentation of ABP (N=16); and (2) spontaneous changes in intracranial pressure (ICP) during plateau waves (N=14). Secondarily, we assessed nCPPs in a larger cohort in which CPP presented a wider range of values. The average correlation in the time domain between CPP and nCPPs for patients undergoing an induced rise in arterial blood pressure (ABP) was 0.95±0.07. For the greater traumatic brain injury (TBI) cohort, this correlation was 0.63±0.37. ∆ correlations between mean values of CPP and nCPPs were 0.73 (p=0.002) and 0.78 (p<0.001) respectively for induced rise in ABP and ICP plateau wave cohorts. The area under the curve (AUC) for ∆CPP was of 0.71 with a 95% confidence interval of 0.54-0.88. To detect low CPP, AUC was 0.817 with a 95% confidence interval of 0.79-0.85. nCPPs can reliably identify changes in direct CPP across time and the magnitude of these changes in absolute values. The ability to detect changes in CPP is reasonable but stronger for detecting low CPP, ≤70mmHg.

The vasopressor action of angiotensin II (ANG II) in ball pythons (Python regius)

Angiotensin II (ANG II) is part of the renin-angiotensin system (RAS) in vertebrates and exert vasoconstriction in all species studied. The present study examines the vasopressor effect of ANG II in the ball python (Python regius), and examines whether ANG II exert its effect through direct angiotensin receptors or through an activation of α-adrenergic receptors. The studies were conducted in snakes with chronic arterial catheters that had recovered from anesthesia. In addition to demonstrating a clear and pronounced dose-dependent rise in arterial blood pressure upon repeated injections of boluses with ANG II (0.001–1 μg/kg), we demonstrate that the pressor response persisted following α-adrenergic blockade using the α-adrenergic antagonist phentolamine (2.5 mg/kg). Unfortunately, it proved impossible to block the ANG receptors using losartan (1, 3 or even 10 mg/kg). The pressor response to ANG II was associated with a significant rise in heart rate at the higher dosages, pointing to a resetting of the barostatic mechanism for heart rate regulation. The responses were similar in fasting and digesting pythons despite the expected rise in baseline values for blood pressure and heart rate of the digesting snakes.

Endogenous Bufadienolide, Blood Pressure and Alcohol Withdrawal.

Previously, it was demonstrated that marinobufagenin (MBG) is implicated in the development of ethanol withdrawal in rats. It has been shown that ethanol withdrawal is associated with a pressor response in the alcoholics. We hypothesized that elevated levels of sodium pump ligand, MBG, would underline the increase in systolic blood pressure during alcohol withdrawal in humans. The cohort included 9 patients with the diagnosis "alcohol dependence syndrome" (F10.(1-3) according to ICD-10). The blood samples for measurement of MBG concentration were collected from the subjects on the first day of withdrawal and after 7 days treatment of the abstinence. Arterial blood pressure was measured via plethysmography at the same time points. The beginning of the alcoholic abstinence was associated with the rise of arterial blood pressure with enhanced levels of plasma MBG. At day 7 following withdrawal, the systolic blood pressure and MBG levels were decreased to normal values. The development of alcohol withdrawal is accompanied by an increase in arterial blood pressure, which is associated with increased plasma MBG concentration.

Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.

The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. We have previously demonstrated that H2O2 is elevated in the kidneys of SS rats. The present study showed a significant upregulation of renal mTORC1 activity in the SS rats fed a 4.0% NaCl for 3 days. In addition, renal interstitial infusion of H2O2 into salt-resistant Sprague Dawley rats for 3 days was also found to stimulate mTORC1 activity independent of a rise of arterial blood pressure. Together, these data indicate that the salt-induced increases of renal H2O2 in SS rats activated the mTORC1 pathway. Daily administration of rapamycin (IP, 1.5 mg/kg per day) for 21 days reduced salt-induced hypertension from 176.0±9.0 to 153.0±12.0 mm Hg in SS rats but had no effect on blood pressure salt sensitivity in Sprague Dawley treated rats. Compared with vehicle, rapamycin reduced albumin excretion rate in SS rats from 190.0±35.0 to 37.0±5.0 mg/d and reduced the renal infiltration of T lymphocytes (CD3+) and macrophages (ED1+) in the cortex and medulla. Renal hypertrophy and cell proliferation were also reduced in rapamycin-treated SS rats. We conclude that enhancement of intrarenal H2O2 with a 4.0% NaCl diet stimulates the mTORC1 pathway that is necessary for the full development of the salt-induced hypertension and kidney injury in the SS rat.

Vasopressin V1a receptors mediate the hypertensive effects of [Pyr1 ]apelin-13 in the rat rostral ventrolateral medulla.

Key points Dysfunctions in CNS regulation of arterial blood pressure lead to an increase in sympathetic nerve activity that participates in the pathogenesis of hypertension.The apelin‐apelin receptor system affects arterial blood pressure homeostasis; however, the central mechanisms underlying apelin‐mediated changes in sympathetic nerve activity and blood pressure have not been clarified.We explored the mechanisms involved in the regulation of [Pyr1]apelin‐13‐mediated cardiovascular control within the rostral ventrolateral medulla (RVLM) using selective receptor antagonists.We show that [Pyr1]apelin‐13 acts as a modulating neurotransmitter in the normotensive RVLM to affect vascular tone through interaction with the vasopressin V1a receptor but that [Pyr1]apelin‐13‐induced sympathoexcitation is independent of angiotensin II receptor type 1, oxytocin, ionotropic glutamate and GABAA receptors.Our data confirm a role for the apelin peptide system in cardiovascular regulation at the level of the RVLM and highlight that this system is a possible potential therapeutic target for the treatment of hypertension. Apelin is a ubiquitous peptide that can elevate arterial blood pressure (ABP) yet understanding of the mechanisms involved remain incomplete. Bilateral microinjection of [Pyr1]apelin‐13 into the rostral ventrolateral medulla (RVLM), a major source of sympathoexcitatory neurones, increases ABP and sympathetic nerve activity. We aimed to investigate the potential involvement of neurotransmitter systems through which the apelin pressor response may occur within the RVLM. Adult male Wistar rats were anaesthetized and ABP was monitored via a femoral arterial catheter. Bilateral RVLM microinjection of [Pyr1]apelin‐13 significantly increased ABP (9 ± 1 mmHg) compared to saline (−1 ± 2mmHg; P < 0.001), which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 ± 1 mmHg; P < 0.01). The rise in ABP was associated with an increase in the low frequency spectra of systolic BP (13.9 ± 4.3% total power; P < 0.001), indicative of sympathetic vasomotor activation. The [Pyr1]apelin‐13‐mediated pressor response and the increased low frequency spectra of systolic BP response were fully maintained despite RVLM pretreatment with the angiotensin II type 1 receptor antagonist losartan, the oxytocin receptor antagonist desGly‐NH2, d(CH2)5[D‐Tyr2,Thr4]OVT, the ionotropic glutamate receptor antagonist kynurenate or the GABAA antagonist bicuculline (P > 0.05). By contrast, the [Pyr1]apelin‐13 induced pressor and sympathoexcitatory effects were abolished by pretreatment of the RVLM with the vasopressin V1a receptor antagonist, SR 49059 (−1 ± 1 mmHg; 1.1 ± 1.1% total power, respectively; P < 0.001). These findings suggest that the pressor action of [Pyr1]apelin‐13 in the RVLM of normotensive rats is not mediated via angiotensin II type 1 receptor, oxytocin, ionotropic glutamate or GABAA receptors but instead involves a close relationship with the neuropeptide modulator vasopressin.

The impact of an experimentally induced increase in arterial blood pressure on left ventricular twist mechanics.

The effects of isometric hand-grip exercise (IHG) coupled with a period of postexercise circulatory occlusion (OCC; known to sustain exercise-induced increases in blood pressure while facilitating a decrease in heart rate) on left ventricular (LV) twist mechanics was examined. Two-dimensional speckle-tracking echocardiography was used to assess LV apical and basal rotation and LV twist in 19 healthy participants (23 ± 2 years old) at rest, during 3 min of IHG (performed at 40% maximal voluntary contraction) and 3 min of OCC immediately following IHG. The IHG elicited significant (P < 0.001) increases in mean arterial pressure (rest, 91 ± 1 mmHg; IHG, 122 ± 2 mmHg) and heart rate (rest, 65 ± 2 beats min(-1); IHG, 91 ± 4 beats min(-1)). Mean arterial pressure remained elevated during OCC (116 ± 2 mmHg; P < 0.001 versus rest), whereas heart rate returned to resting levels (68 ± 3 beats min(-1); P = 0.159 versus rest). Apical rotation decreased significantly (P < 0.01) by 10 ± 5% during IHG and 21 ± 4% during OCC, whereas basal rotation remained unchanged from rest. Left ventricular twist decreased from rest to IHG (12 ± 5%; P = 0.015) and OCC (21 ± 4%; P = 0.001), whereas a decrease in LV untwist rate was observed only during OCC. An increase in blood pressure generated by IHG, and maintained by a period of OCC, impairs aspects of LV twist mechanics. Postexercise circulatory occlusion isolated the effect of the arterial blood pressure rise (from heart rate), magnifying the impairment of LV twist mechanics when compared with IHG, whilst also negatively impacting LV relaxation. We propose that a protocol using isometric exercise followed by circulatory occlusion provides a method for studying the effects of blood pressure changes on LV twist mechanics.

Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

Endoplasmic reticulum and oxidant stress mediate nuclear factor-κB activation in the subfornical organ during angiotensin II hypertension.

Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the brain circumventricular subfornical organ (SFO) mediate the central hypertensive actions of Angiotensin II (ANG II). However, the downstream signaling events remain unclear. Here we tested the hypothesis that angiotensin type 1a receptors (AT1aR), ER stress, and ROS induce activation of the transcription factor nuclear factor-κB (NF-κB) during ANG II-dependent hypertension. To spatiotemporally track NF-κB activity in the SFO throughout the development of ANG II-dependent hypertension, we used SFO-targeted adenoviral delivery and longitudinal bioluminescence imaging in mice. During low-dose infusion of ANG II, bioluminescence imaging revealed a prehypertensive surge in NF-κB activity in the SFO at a time point prior to a significant rise in arterial blood pressure. SFO-targeted ablation of AT1aR, inhibition of ER stress, or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase in SFO NF-κB. These findings highlight the utility of bioluminescence imaging to longitudinally track transcription factor activation during the development of ANG II-dependent hypertension and reveal an AT1aR-, ER stress-, and ROS-dependent prehypertensive surge in NF-κB activity in the SFO. Furthermore, the increase in NF-κB activity before a rise in arterial blood pressure suggests a causal role for SFO NF-κB in the development of ANG II-dependent hypertension.

Abstract W P165: Acetaminophen Use and Risk of Stroke and Myocardial Infarction in a Hypertensive Population

Introduction: Recent data suggest self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest rise in arterial blood pressure. There are no randomized studies, studies using verified prescription data or studies in high risk patients that investigate this relationship. Hypothesis: We aimed to assess the relationship between acetaminophen prescription data and risk of stroke and myocardial infarction in patients with hypertension. Methods: We performed a retrospective data analysis using data contained within the UK Clinical Research Practice Datalink. This includes verified prescription data. Multivariable Cox proportional hazard models were used to estimate hazard ratios for stroke or MI associated with acetaminophen use over a 10-year period. Acetaminophen exposure was a time dependent variable. A propensity matched design was also used to reduce potential for confounding. Results: We included 24496 hypertensive individuals aged 65-years or older. Of these, 10878 were acetaminophen exposed and 13618 were not. There was no relationship between risk of stroke, MI or any vascular event and acetaminophen exposure on adjusted analysis (OR 1.09, 95% CI 0.86 to 1.38; OR 0.98, 95% CI 0.76 to 1.27; OR 1.17, 95% CI 0.99 to 1.37 respectively). Results in the propensity matched sample (n=4000 per group) were similar and high frequency users (defined as receiving a prescription for &gt;75% of months) were also not at increased risk. Conclusions: In summary, use of acetaminophen was not associated with an increased risk of stroke or myocardial infarction in a large cohort of hypertensive patients.

Evolving blood pressure dynamics for extremely preterm infants

ObjectiveTo examine changes in arterial blood pressure (ABP) after birth in extremely preterm infants.Study DesignProspective observational study of infants 230/7 – 266/7 weeks gestational age (GA). Antihypotensive therapy use and ABP measurements were recorded for the first 24 hours.ResultsA cohort of 367 infants had 18,709 ABP measurements recorded. ABP decreased for the first three hours, reached a nadir at 4 – 5 hours, then increased at an average rate of 0.2 mmHg / hour. The rise in ABP from hour 4 – 24 was similar for untreated infants (n=164) and infants given any antihypotensive therapy (n=203), a fluid bolus (n=135), or dopamine (n=92). GA specific trends were similar. ABP tended to be lower as GA decreased, but varied widely at each GA.ConclusionArterial blood pressure increased spontaneously over the first 24 postnatal hours for extremely preterm infants. The rate of rise in ABP did not change with antihypotensive therapy.

Magnesium nitrate attenuates blood pressure rise in SHR rats.

The administration of magnesium supplements and nitrates/nitrites decreases arterial blood pressure and attenuates the development of hypertension-induced complications. This study was performed to examine the effects of treatment with magnesium nitrate on the development of hypertension and its complications in spontaneously hypertensive (SHR) rats. Male SHR rats with persistent hypertension at the age of 12-13 weeks were allocated to two groups according to their arterial blood pressure. Rats from the control group received purified water, while the experimental animals from the second group received magnesium nitrate dissolved in purified water at a dose of 50mg/kg. After four weeks of treatment, blood pressure was measured, the anatomical and functional parameters of the heart were recorded using an ultrasonograph, vascular reactivity was assayed in organ bath experiments and the cardioprotective effects of magnesium nitrate administration was assayed in an ex vivo experimental heart infarction model. Treatment with magnesium nitrate significantly increased the nitrate concentration in the plasma (from 62±8 μmol/l to 111±8μmol/L), and attenuated the increase in the arterial blood pressure. In the control and magnesium nitrate groups, the blood pressure rose by 21±3mmHg and 6±4mmHg, respectively. The administration of magnesium nitrate had no effect on the altered vasoreactivity, heart function or the size of the heart infarction. In conclusion, our results demonstrate that magnesium nitrate effectively attenuates the rise in arterial blood pressure. However, a longer period of administration or earlier onset of treatment might be needed to delay the development of complications due to hypertension.

An electrophysiological approach using 3D electroanatomical mapping system for catheter- -based renal denervation: the first Polish experience

We present the case of a 49-year-old male patient with hypertension, coronary artery disease, diabetes mellitus type 2, hyperuricemia and dyslipidaemia. The patient had a history of multiple coronary stenting and previous ischaemic stroke. Despite chronic therapy with six antihypertensive drugs (metoporolol succinate 100 mg, valsartan 160 mg, torasemide 10 mg, spironolactone 25 mg, doxazosinum 8 mg, nitrindipine 20 mg) his arterial blood pressure (BP) remained still elevated (Table 1). He presented frequent episodes of headache, dizziness, and syncope and was also hospitalised due to episodes of hypertensive crisis. The set of endocrinology tests and renal angiography excluded secondary causes of hypertension. Additionally, the scan revealed anatomy of renal arteries favourable for catheter-based renal denervation. Due to highly symptomatic and drug resistant hypertension, the patient was referred for an invasive treatment option as an adjunctive therapy. The procedure was performed in the electrophysiological laboratory. Arterial BP was continuously monitored with a Finometer Pro device (Finapres Medical Systems BV, Amsterdam, The Netherlands). Initially an angiography of the right and left renal arteries was performed through transfemoral access (Fig. 1). Subsequently, the patient underwent 3D electroanatomical mapping (CARTO 3 electroanatomical mapping system, Biosense Webster, Inc., Johnson & Johnson, Diamond Bar, CA, USA) of the aorta and both renal arteries (Fig. 2). Before radiofrequency (RF) current application, we paced 10 s 20 Hz (10 mA/2 ms) burst sequence using a mapping catheter (Navistar Thermocool, Johnson & Johnson) at the ostia of each renal artery as described by Pokushalov et al. (J Am Coll Cardiol, 2012; 60: 1163–1170). Immediately after pacing, a rise of arterial BP was observed (Fig. 3). Afterwards, under intravenous analgesia (midasolam and fentanyl), applications of RF energy (7–8 W; 95–120 s) were delivered in two points in the left renal artery and in four points in the right renal artery (Fig. 2). Subsequent renal arteriography revealed neither stenosis nor dissection. The further in-hospital observation was uneventful. Herein, we present the first Polish experience with renal denervation performed with the electrophysiological method using 3D electroanatomical mapping. This procedure was part of a research project approved by the Ethics Committee, Medical University of Lodz, Poland.

Acetaminophen use and change in blood pressure in a hypertensive population

Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and a rise in arterial blood pressure (BP). We investigated the association between acetaminophen use and BP in a large cohort of patients with hypertension using verified prescription data. We extracted data from the UK General Practice Research Database for all hypertensive patients aged 65 years or older who were prescribed acetaminophen and had BP measured both before and during acetaminophen treatment. Patients were grouped according to whether their antihypertensive treatment remained unchanged or not during the study period. The change in SBP and DBP during acetaminophen use was determined and compared with the change in BP in a group of nonacetaminophen-exposed people identified using propensity matching. A total of 2754 acetaminophen-exposed individuals were included. BP rose slightly during the period of acetaminophen treatment wherein antihypertensive treatment was unchanged [change in SBP 1.6 [95% confidence interval (CI) 0.7-2.5) mmHg and change in DBP 0.5 (95% CI 0.1-1.0) mmHg)]. BP fell when new antihypertensive medications were prescribed. These BP changes were no different to those seen in matched nonacetaminophen-exposed individuals [between-group difference wherein antihypertensive treatment was unchanged was 0.6 (95% CI -0.6 to 1.9) mmHg and 0.5 (-0.1 to 1.1) mmHg for change in SBP and DBP, respectively]. We found no evidence of a sustained rise in blood pressure caused by acetaminophen treatment in a large population of patients with treated hypertension.