Reduction In Peripheral Vascular Resistance Research Articles

Metabolomic Profile and Its Correlation with the Plasmatic Levels of Losartan, EXP3174 and Blood Pressure Control in Hypertensive and Chronic Kidney Disease Patients.

Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and, when dysregulated, may cause serious complications. Losartan (LOS) blocks relevant physiological aspects of hypertension, acting mainly on the reduction of peripheral vascular resistance. Complications of hypertension include nephropathy, in which diagnosis is based on the observation of functional or structural renal dysfunction. Therefore, blood pressure control is essential to attenuate the progression of chronic kidney disease (CKD). In this study, 1H NMR metabolomics were used to differentiate hypertensive and chronic renal patients. Plasmatic levels of LOS and EXP3174, obtained by liquid chromatography coupled with mass-mass spectroscopy, were correlated with blood pressure control, biochemical markers and the metabolomic fingerprint of the groups. Some biomarkers have been correlated with key aspects of hypertension and CKD progression. For instance, higher levels of trigonelline, urea and fumaric acid were found as characteristic markers of kidney failure. In the hypertensive group, the urea levels found could indicate the onset of kidney damage when associated with uncontrolled blood pressure. In this sense, the results point to a new approach to identify CKD in early stages and may contribute to improving pharmacotherapy and reducing morbidity and mortality associated with hypertension and CKD.

Administration of Nitrates After Spontaneous Delivery in Rheumatic Heart Disease

Introduction: Heart disease is one of the most common causes of maternal death. The incidence has increased since women with congenital and acquired heart disease reached fertile age. The circulation system changes during pregnancy which are induced by changes in the progesterone. The changes in progesterone levels increase heart work and cause death in pregnant women. Objective: This report aims to elaborate on the administration of nitrates as the management of labor in rheumatic heart disease (RHD). Case Report: A 27-year-old woman complained of shortness of breath and wanted to give birth. The patient was 38 weeks pregnant and had a history of heart disease. Antero-posterior chest radiography examination showed pulmonary edema and cardiomegaly. The patient was examined using echocardiography before spontaneous labor and was diagnosed as pregnant with rheumatic heart disease. As an emergency management, the patient was given painless spontaneous labor. The patient was given nitrates on the first day after delivery as a treatment for progesterone withdrawal syndrome in this case. After the delivery process was completed, the patient was admitted to the Intensive Care Unit (ICU). Discussion: Progesterone hormone produced by the corpus luteum and the placenta until the eighth week of pregnancy and before delivery, respectively, can reduce systemic vascular resistance. Progesterone hormone increase causes peripheral vasodilation by affecting the function of endothelial nitric oxide synthase (eNOS) and nitrite oxide (NO) production. Conclusion: A pregnant woman with rheumatic heart disease can be given exogenous nitrate. Administration of exogenous nitrates in this patient successfully prevent the reduction of peripheral vascular resistance and postpartum hemodynamic instability because it can replace the reduction in nitric oxide caused by progesterone withdrawal.

Cuffless Blood Pressure Estimation During Moderate- and Heavy-Intensity Exercise Using Wearable ECG and PPG.

To develop and evaluate an accurate method for cuffless blood pressure (BP) estimation during moderate- and heavy-intensity exercise. Twelve participants performed three cycling exercises: a ramp-incremental exercise to exhaustion, and moderate and heavy pseudorandom binary sequence exercises on an electronically braked cycle ergometer over the course of 21 minutes. Subject-specific and population-based nonlinear autoregressive models with exogenous inputs (NARX) were compared with feedforward artificial neural network (ANN) models and pulse arrival time (PAT) models. Population-based NARX models, (applying leave-one-subject-out cross-validation), performed better than the other models and showed good capability for estimating large changes in mean arterial pressure (MAP). The models were unable to track consistent decreases in BP during prolonged exercise caused by reduction in peripheral vascular resistance, since this information is apparently not encoded in the employed proxy physiological signals (electrocardiography and forehead PPG) used for BP estimation. Nevertheless, the population-based NARX model had an error standard deviation of 11.0 mmHg during the entire exercise window, which improved to 9.0 mmHg when the model was periodically calibrated every 7 minutes. Population-based NARX models can estimate BP during moderate- and heavy-intensity exercise but need periodic calibration to account for the change in vascular resistance during exertion. MAP can be continuously tracked during exercise using only wearable sensors, making monitoring exercise physiology more convenient and accessible.

Effect Of Restorative Massage On Regional Blood Flow In Paralympic Athletes

Objective — to evaluate an impact of a restorative massage course, integrated into a training session, on the regional blood circulation in Paralympic athletes. Materials and Methods — Athletes with impaired musculoskeletal system (IMSS), shooters and powerlifters (n=23), were subjected to a course of restorative massage in a special preparatory microcycle of the competitive period. In the main group, massage sessions were included in the training session, whereas in the control group, they were conducted at the end of the training session. The evaluation of peripheral circulation in the upper limbs was performed via vascular blood flow test; and the effectiveness of arterial and venous blood flow, vascular tone and elasticity were assessed. Results — The obtained results for the first time allowed describing the effect of restorative massage on the peripheral circulation of Paralympic athletes. After a course of restorative massage was integrated into a training session, changes in peripheral hemodynamics were noted. We revealed an improvement in arterial blood flow due to an increase in the time of rapid blood filling, a decrease in the tone of medium and small vessels, and a reduction in peripheral vascular resistance (PVR). Arterial and venous blood flow at the level of postcapillaries improved in all segments. The blood flow was effectively redistributed between the distal and proximal segments of the upper limbs. Conclusion — The use of massage sessions in the middle of a training session has a positive effect on the state of peripheral circulation in the proximal upper limbs and the tone of large vessels, whereas the use of massage at the end of a workout has a predominant effect on the tone of small vessels and the state of blood circulation in distal segments of the limbs.

Effect of cycle ergometry on peripheral blood flow, vascular conductance, and vascular resistance in young people

IntroductionThe study aimed to evaluate haemodynamic changes in peripheral blood flow, vascular conductance (VC), and peripheral vascular resistance (PVR) in healthy individuals undergoing passive and active lower limb cycle ergometry.MethodsThis was a prospective, controlled, randomized study with a crossover design, in which 14 normotensive volunteers were allocated to receive: (1) assessment without intervention (control group); (2) passive lower limb cycle ergometry; and (3) active cycle ergometry of lower limbs. In the physical exercise session of the active and passive lower limb cycle ergometry protocol, the volunteers were placed in the supine position and then performed aerobic exercise for 20 minutes. Forearm blood flow was measured with a venous occlusion plethysmograph, blood pressure was evaluated with oscillometric and automatic equipment, and heart rate was monitored continuously through lead II of electrocardiogram.ResultsActive cycle ergometry was able to promote hypotension after physical exercise owing to a reduction in mean blood pressure (<i>p</i> = 0.000), with an improvement in vascular function as reflected by a reduction in PVR (<i>p</i> = 0.000) and an increase in VC (<i>p</i> = 0.000). Although the reduction in mean blood pressure in the passive cycle ergometry group was not significant, it was sufficient to promote an increase in VC (<i>p</i> = 0.049) and a reduction in PVR (<i>p</i> = 0.008).ConclusionsA single session of 20 minutes of physical exercise with passive or active cycle ergometry of the lower limbs was sufficient to promote haemodynamic changes in normotensive individuals.

Effects of Exercise Training on PPARβ/δ Expression in Skeletal Muscle of Rats with Spontaneous Hypertension.

ABSTRACTPurposeThis study aimed to identify the relationship and mechanism between skeletal muscle peroxisome proliferator–activated receptor β/δ (PPARβ/δ) and spontaneous hypertension.MethodsRats were divided into four groups (n = 10): spontaneous hypertensive rats exercise group (SHR-E), spontaneous hypertensive rats sedentary group (SHR-S), Wistar-Kyoto control rats exercise group (WKY-E), and Wistar-Kyoto control rats sedentary group (WKY-S). Although the sedentary groups were placed on the treadmill without moving during the training sessions, the exercise groups were forced to run on a treadmill for 8 wk, 1 h·d−1, 5 d·wk−1. After training, the density and area of gastrocnemius microvessels were observed. PPARβ/δ, vascular endothelial growth factor A (VEGFA), superoxide dismutase 2 (SOD-2), and nitric oxide synthase in gastrocnemius were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot.ResultsExcept the sixth week of age, the systolic blood pressure of SHR-S was significantly higher than that of WKY-S at all time periods. Exercise significantly reduced systolic blood pressure in SHR rats. Compared with the SHR-S group, the WKY-S group had significantly higher PPARβ/δ protein level and density of skeletal muscle microvessels. Eight weeks of exercise increased the PPARβ/δ, SOD-2, VEGFA, and microvessel density and area in the skeletal muscle of SHR.ConclusionsExercise training promoted PPARβ/δ mRNA and protein-level expression of PPARβ/δ, SOD-2 and VEGFA in skeletal muscle, thus increasing the density and area of skeletal muscle blood vessels. These regulations contribute to the reduction of peripheral vascular resistance. This may be a potential mechanism of exercise to reduce blood pressure.

Impact of cardiovascular risk factors in vascular remodelling of pregnant women

Abstract Introduction Pregnancy is a physiological condition of hemodynamic overload, characterized by a progressive reduction of peripheral vascular resistance, which normalizes postpartum. Purpose To characterize arterial stiffness and endothelial function during pregnancy and postpartum and to investigate the impact of cardiovascular (CV) risk factors. The secondary aim was to explore the potential association between pulse wave velocity (PWV) and risk for preeclampsia. Methods Prospective cohort study including volunteer pregnant women (healthy, obese and/or hypertensive) recruited in a tertiary centre between 2019 and 2020, at their 1st or 3rd trimester of pregnancy. Women were evaluated at the first trimester [10–15 weeks, baseline], third trimester [30–35 weeks, peak of CV remodelling] of pregnancy as well as at the 1st month and 6th month after delivery (CV reverse remodelling stages). The evaluation included clinical characterization through questionnaires as well as arterial stiffness and endothelial assessment by PWV and EndoPAT, respectively. Kruskal-Wallis H test and Friedman test were used as appropriate to between and within groups comparisons. Bonferroni correction was applied. Spearman correlation was performed to determine the relationship between PWV and risk for preeclampsia. Results We included 34 pregnant women with a median age of 34 [26; 41]years, 50% being hypertensive and/or obese. Arterial stiffness decreased significantly from the 1st to the 3rd trimester (6.3 [5.3 to 7.8] cm/s vs 5.6 [4.9 to 7.3] cm/s, p<0.001), normalizing only at the 6th months (5.6 [4.9 to 7.3] cm/s vs 6.3 [5.5 to 8.3] cm/s, p=0.001). A significant deterioration of endothelial function became evident from 1st to 3rd trimester (logarithm of reactive hyperemia index [lnRHI]: 0.74 [0.05 to 1.20] vs 0.45 [0.22 to 0.79], p=0.020). However, its slight amelioration begun only 6 months after delivery (3rd trimester: lnRHI 0.45 [0.22 to 0.79] vs 6 months at postpartum: lnRHI 0.53 [0.10 to 1.01], p>0.99). Compared to the healthy pregnant women, the CV risk factors group showed a higher pulse wave velocity only at the peak of CV remodelling (5.6 [5.3 to 7.3] cm/s vs 5.6 [4.9 to 7.2] cm/s, p=0.016), without any other differences in other parameters of time points evaluated. Pulse wave velocity at the first trimester revealed a positive association with risk for preeclampsia (r=0.485, p=0.026). Conclusion Our cohort presented a significant decrease in vascular resistance during pregnancy and normalization at the 6th month after delivery. Pregnant women with cardiovascular risk factors showed an increased arterial stiffness in the 3rd trimester compared to healthy pregnant women. Pulse wave velocity correlated positively with the risk for preeclampsia. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Universidade do Porto/FMUP and FSE-Fundo Social Europeu; FCT - Foundation for Science and Technology

Cardiovascular Effects Induced by Fruit Peels from Passiflora edulis in Hypertensive Rats and Fingerprint Analysis by HPLC-ESI-MSn spectrometry.

Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis. Glycoside flavonoids were identified in the extract by HPLC-ESI-MSn. The extract showed a significant hypotensive effect after 28days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P.edulis. Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension.

Maternal cardiac function in women at high risk for pre-eclampsia treated with 150mg aspirin or placebo: an observational study.

To compare maternal haemodynamics in women at low and high risk for preterm pre-eclampsia (PE), and between those at high risk who are randomised to aspirin or placebo. Prospective, longitudinal observational study. Maternity units in six UK hospitals. Women participating in the Aspirin for Prevention of Preterm Pre-eclampsia (ASPRE) trial. The population comprised three groups of women: low risk for preterm PE (n=1362), high risk for preterm PE treated with aspirin (n=208) and high risk for preterm PE on placebo (n=220). Women had four visits during pregnancy: 11-14, 19-24, 30-34, and 35-37weeks' gestation. Blood pressure was measured with a device validated for pregnancy, and PE and maternal haemodynamics were assessed with a bioreactance monitor at each visit. A multilevel linear mixed-effects analysis was performed to examine longitudinal changes of maternal haemodynamic variables, controlling for demographic characteristics, past medical history and medication use. Longitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR). The low-risk group demonstrated the expected changes with an increase in CO and reduction in MAP and PVR, with a quadratic change across gestation. In contrast, the high-risk groups had a declining CO, and higher MAP and PVR during pregnancy. The administration of aspirin did not appear to affect maternal haemodynamics. Women screened as high risk for preterm PE have a pathological cardiac adaptation to pregnancy and the prophylactic use of aspirin (150mg oral daily from the first trimester) in this group may not alter this haemodynamic profile. In women at high risk of pre-eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.

Mechanisms Underlying Obesity‐Related Hypertension: An Experimental Weight Gain Study in Humans

BackgroundThe association between body size and blood pressure (BP) is well recognised. However, not all overweight individuals have elevated BP suggesting that important adaptive mechanisms are present in some. Cardiac output (CO, a key determinant of BP, is elevated in young overweight individuals, but is not associated with the level of BP. However, peripheral vascular resistance (PVR) is associated with the level of BP in these individuals, suggesting that the ability to modulate PVR in response to increased CO is important.ObjectiveWe hypothesized that weight gain increases CO in healthy humans and that the ability of the peripheral vasculature to adapt to this increase determines BP. Therefore, we undertook an exploratory study of experimental weight gain in healthy young adults.MethodsSixteen healthy non‐obese males were recruited (mean±SD age 29±6 years). All participants were overfed approximately 1000kcal/day, alongside their normal diet, for 6–8 weeks, until a weight gain of 5kg was achieved and held stable for at least 1 week. Detailed anthropometric characteristics, BP, CO and PVR were assessed at baseline and at completion of the overfeeding intervention.ResultsOverfeeding resulted in a significant increase in body weight (6.11±3.08kg, P<0.001), lean mass (3.61±3.40kg, P=0.001) and fat mass (2.64±2.89kg, P=0.002). The increases in systolic BP (2±9mmHg) and diastolic BP (2±6mmHg) were not significant (P<0.2 for both) and the increase in heart rate was of borderline significance (5±10bpm, P=0.055). As hypothesised, there was a significant increase in cardiac output (0.81±1.35L/min, P=0.031), which was accompanied by a decrease in PVR (129±205dynes.sec.cm5, P=0.024). Dichotomising individuals on the basis of a systolic BP response to weight gain of ≥5mmHg (BP responders) revealed small differences vs non‐responders in the change in CO (+1.34±0.99L/min vs +0.4±1.50L/min) and PVR (−111±142 dynes.sec.cm5 vs −143±251 dynes.sec.cm5), although neither comparison was statistically significant.ConclusionsModest weight gain in healthy, non‐obese men is associated with an increase in both lean and fat tissue mass. A compensatory reduction in PVR in response to elevated cardiac output is likely to explain the lack of change in BP. Examining ‘responders’ versus ‘non responders’ in terms of BP change in response to weight gain is likely to provide useful insights into obesity‐associated hypertension in a larger trial.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets.

Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl Cotransporter (NCC) in the Distal Convoluted Tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of antihypertensive effect of thiazides. It is plausible that both mechanisms, renal and extra-renal, may be operating simultaneously. Recent studies point to compensatory mechanisms in the kidney distal nephron that may play a role in blunting the diuretic effect of thiazides. Not much information is available about the efficacy of thiazides in controlling blood pressure in individuals with Chronic Kidney Disease (CKD). This review will discuss the latest updates on the use and efficacy of thiazides derivatives as diuretics and antihypertensive medications in CKD patients. Thiazides remain effective as diuretics and antihypertensive agents in individuals with low GFR.

Celosia argentea L. (Amaranthaceae) a vasodilator species from the Brazilian Cerrado – An ethnopharmacological report

Ethnopharmacological relevanceCelosia argentea L. (Amaranthaceae), popularly known as “crista de galo”, is used in folk medicine due to its diuretic and hypotensive effects. However, there are no reports in the literature regarding its pharmacological effects on the cardiovascular system as well as no data proving the safety of this species. AimTo perform a detailed ethnopharmacological investigation of the ethanol soluble fraction from C. argentea (ESCA) using male and female Wistar rats. Material and methodsFirstly, a morpho-anatomical characterization was performed to determine the quality control parameters for the identification of the species under investigation. Then, the ethanol extract was obtained and chemically characterized by LC-DAD-MS. Furthermore, an oral acute toxicity study was performed in female Wistar rats. Finally, the possible diuretic and hypotensive effects of three different doses of ESCA (30, 100 and 300 mg/kg) were evaluated in male Wistar rats. Besides, the vasodilatory response of ESCA in mesenteric vascular beds (MVBs) and its involvement with nitric oxide/cGMP and prostaglandin/cAMP pathways as well as potassium channels were evaluated. ResultsThe main secondary metabolites present in ESCA were phenolic compounds, megastigmanes and triterpenoid saponins. ESCA caused no toxic effects in female rats nor increased urinary excretion in male rats after acute administration. However, ESCA significantly increased the renal elimination of potassium and chloride, especially at the end of 24 h after administration. Intermediary dose (100 mg/kg) of ESCA was able to promote significant acute hypotension and bradycardia. Moreover, its cardiovascular effects appear to be involved with the voltage-dependent K+ channels activation in MVBs. ConclusionThis study has brought new scientific evidence of preclinical efficacy of C. argentea as a hypotensive agent in normotensive rats. Apparently, these effects are involved with the activation of the voltage-sensitive K+ channels contributing to the reduction of peripheral vascular resistance and cardiac output.

Hypotensive, vasorelaxant and antihypertensive activities of the hexane extract of Anacardium occidentale Linn

Anacardium occidentale is widely used in folk medicine in Brazil, India, and Africa to treat inflammation, diabetes and hypertension. The aim of the study was to assess the hypotensive, vasorelaxant and antihypertensive effects produced by the hexane extract from the leaves of A. occidentale (HEAO) in rats. The animals were anesthetized, and polyethylene catheters were embedded into the lower abdominal aorta and the inferior vena cava for blood pressure measurements and drug administration. The HEAO was injected and the mean arterial pressure and heart rate were measured. The effects of the HEAO on isolated rat mesenteric rings with and without endothelium were investigated. HEAO induced hypotension and bradycardia in normotensive rats. After pretreatment with L-NAME, indomethacin, atropine or hexamethonium, these effects were attenuated. In mesenteric rings, HEAO antagonized the contractile effects induced by phenylephrine or KCl. This effect was inhibited after removal of the vascular endothelium. Oral administration of the HEAO decreased significant mean arterial pressure in spontaneously hypertensive rats. Mass spectrometric analysis of HEAO identified malic acid and quercetin. Our findings demonstrate that HEAO produces hypotension probably due to a reduction in peripheral vascular resistance, mediated by the endothelium, in part, by a decrease in cardiac output. Bradycardia appears to be due to the indirect activation of cardiac muscarinic receptors via activation of the vagus nerve. The HEAO also induces an antihypertensive effect.

Estrogenic vascular effects are diminished by chronological aging

The beneficial role of estrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of estrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of aging and the menopause on the acute vasodilatory effects of estrogen using ex vivo human and murine resistance arteries. Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre- (42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Aging was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodeling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-estradiol (non-specific estrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by aging and the menopause. However, the impairment of estrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that chronological resistance arterial aging is a prominent factor leading to weakened vasodilatory action of estrogenic compounds.

Cardiac sympathetic afferent reflex control of cardiac function in normal and chronic heart failure states.

Cardiac sympathetic afferents are considered to be essential pathways for transmission of cardiac nociception to the central nervous system during myocardial ischaemia. However, a potential contribution of the CSAR control of cardiac dysfunction in both normal and chronic heart failure (CHF) states remains unknown. We found that activation of the CSAR evokes little increase in cardiac contractility with an exaggerated peripheral vasoconstriction in the CHF state. CSAR inhibition by epicardial lidocaine decreased cardiac contractility to a greater extent in CHF rats than sham rats. Furthermore, we also found that epicardial lidocaine paradoxically decreased left ventricular end-diastolic pressure (LVEDP) and left ventricular end-diastolic volume (preload) in CHF rats, which was not observed in sham rats. Chronic ablation of the CSAR by epicardial application of the afferent neurotoxin, RTX, selectively lowered diastolic blood pressure CHF rats. The observation suggests that CSAR has a differential effect on cardiac function in normal and CHF states. CSAR activation in normal state causes significant increase in cardiac contractility and cardiac output. The enhanced 'cardiac sympathetic afferent reflex' (CSAR) critically contributes to the exaggerated global sympathetic tone in chronic heart failure (CHF). However, a potential contribution of the cardio-cardiac reflex control of cardiac function in both normal and CHF states remains unknown. In this study, we evaluated the effects of direct activation or inhibition of the CSAR on cardiac function by pressure-volume (P-V) loop analysis in ∼12-week sham-operated and myocardial infarcted (MI) rats. In sham rats, acute CSAR activation by epicardial application of bradykinin (BK) increased heart rate (HR), left ventricular systolic pressure (LVSP), the maximum first derivative of left ventricular pressure (dp/dtmax ), and the slope of the end-systolic P-V relationship (ESPVR), suggesting that acute CSAR activation in the normal state enhances myocardial contractility. CSAR activation also decreased left ventricular (LV) systolic and diastolic volumes with little effect on LV end-diastolic pressure (LVEDP) or the end-diastolic P-V relationship (EDPVR) in sham rats. Compared to sham, CHF rats exhibit a reduced increase in the slope of the ESPVR and dp/dtmax in response to BK, indicating a poor contractile response to CSAR activation. Interestingly, BK application in CHF rats increased cardiac systolic and diastolic volumes and further increased the elevated LVEDP, neither of which was seen in sham rats. Following CSAR inhibition by epicardial lidocaine, blood pressure, HR, LVSP, dp/dt, LVEDP and ESPVR decreased in CHF rats whereas lidocaine had little effect in sham rats, indicating that the CSAR is tonically active in CHF and contributes to cardiac dysfunction. Furthermore, we found that epicardial lidocaine paradoxically decreased LV end-diastolic volume (preload) in CHF rats, which was not observed in sham rats. The decreased preload by lidocaine in CHF rats may be due to a reduction in peripheral vascular resistance since epicardial lidocaine significantly lowered peripheral (renal) sympathetic nerve activity in CHF rats but not in sham rats. Furthermore, chronic ablation of CSAR by epicardial application of a selective afferent neurotoxin, resiniferatoxin, selectively lowered diastolic blood pressure both at daytime and night-time with less effect on systolic blood pressure in CHF rats. Our data suggest that there is an imbalance between cardiac and peripheral responses to CSAR in CHF animals compared to sham-operated controls.

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

BackgroundA family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise.ObjectiveTo test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.MethodsThe study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®).ResultsAt rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03).ConclusionNormotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

Pharmacological implications of the Ca(2+)/cAMP signaling interaction: from risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders.

In this review, we discussed pharmacological implications of the Ca2+/cAMP signaling interaction in the antihypertensive and neurological/psychiatric disorders therapies. Since 1975, several clinical studies have reported that acute and chronic administration of L-type voltage-activated Ca2+ channels (VACCs) blockers, such as nifedipine, produces reduction in peripheral vascular resistance and arterial pressure associated with an increase in plasma noradrenaline levels and heart rate, typical of sympathetic hyperactivity. Despite this sympathetic hyperactivity has been initially attributed to adjust reflex of arterial pressure, the cellular and molecular mechanisms involved in this apparent sympathomimetic effect of the L-type VACCs blockers remained unclear for decades. In addition, experimental studies using isolated tissues richly innervated by sympathetic nerves (to exclude the influence of adjusting reflex) showed that neurogenic responses were completely inhibited by L-type VACCs blockers in concentrations above 1 μmol/L, but paradoxically potentiated in concentrations below 1 μmol/L. During almost four decades, these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical increase in sympathetic activity produced by L-type VACCs blocker is due to interaction of the Ca2+/cAMP signaling pathways. Then, the pharmacological manipulation of the Ca2+/cAMP interaction produced by combination of the L-type VACCs blockers used in the antihypertensive therapy, and cAMP accumulating compounds used in the antidepressive therapy, could represent a potential cardiovascular risk for hypertensive patients due to increase in sympathetic hyperactivity. In contrast, this pharmacological manipulation could be a new therapeutic strategy for increasing neurotransmission in psychiatric disorders, and producing neuroprotection in the neurodegenerative diseases.

Cardiac dysfunction in patients with cirrhosis: is the systolic component its main feature?

To investigate the subclinical cardiac morphological and functional modifications in cirrhotic patients according to the stage of liver disease. One hundred and thirteen cirrhotic patients underwent standard Doppler echocardiography and were compared with healthy individuals. Left ventricular (LV) geometry, systolic/diastolic function, and the main hemodynamic parameters were assessed according to current guidelines. Cirrhotic patients showed a reduction in the peripheral vascular resistance (PVR), a compensatory hyperdynamic syndrome, and a significant increase in cardiac index (CI), cardiac output (CO), and cardiac work, with a consequent increase in the prevalence of LV hypertrophy and associated diastolic dysfunction (DD). Age (P=0.005) and LV mass index (P=0.03) were the strongest predictors of DD. Even though all the systolic parameters assessed were similar between patients and controls, in patients with refractory ascites, the reduction of the PVR and mean blood pressure was not balanced by a further increase in cardiac work and therefore the CI and CO were supported only by the increase in heart rate. In cirrhotic patients, DD is strongly related to the increase in LV mass, not related to the stage of the liver disease, and can be correctly detectable only by the use of tissue Doppler imaging. For systolic dysfunction, along with the development and worsening of ascites, CO and CI do not increase further to compensate the continuous reduction of PVR and mean blood pressure, and their maintenance becomes critically dependent on the heart rate, thus suggesting a possible detrimental effect of β-blockers in these patients.

PP.14.15

Objective: Vasodilators are clinically used in accordance with each pharmacological property. For example, Ca2+ channel blockers are prescribed for patients with hypertension, which dilate arterioles leading to reduction of peripheral vascular resistance. Organic nitrates are used for the treatment of various cardiovascular diseases including angina and heart failure to reduce ventricular preload and afterload, which dilates all segments of the vascular system from large conductance arteries to large veins. Since useful indexes reflecting vascular functions of larger conductance arteries are unavailable using non-invasive methods in contrast to the resistant arteries, we assessed whether the cardio-ankle vascular index (CAVI), established as a marker of arterial stiffness, could reflect different pharmacological actions of nicardipine and nitroglycerin on the systemic vasculature in anesthetized rabbits. Design and method: New Zealand White rabbits were anesthetized with halothane. The CAVI was calculated from the well-established basic equations obtained from the variables of brachial and tibial blood pressure and phonocardiogram. Results: Intravenous administration of nicardipine (1, 3 and 10 μg/kg) decreased the blood pressure, femoral arterial vascular resistance, and heart-ankle pulse wave velocity (haPWV) in a dose-dependent manner. Meanwhile, no significant change was detected in the CAVI at 1 and 3 μg/kg, which reflect the defining feature that CAVI is independent of blood pressure. At the highest dose of 10 μg/kg, the index increased. Intravenous administration of nitroglycerin (2, 4 and 8 μg/kg) also decreased the blood pressure, femoral arterial vascular resistance, and haPWV in a dose-dependent manner. Meanwhile, the CAVI decreased in a dose-dependent manner, which may reflect the pharmacological action that nitroglycerin dilates conductance arteries. Conclusions: These results suggest that CAVI is a useful index that can differentiate pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbit.

Effects of Hydrogen Sulfide on Circulation

Hydrogen sulfide (H2S) has been suggested to relax the vascular smooth muscles and produce a vasodilation. However, it remains unclear whether endogenous H2S produced in the vessels, if any, can produce a vasodilatory effect, which has a relevant physiological or clinical meaning, as concentrations of H2S used in vitro to produce these effects are within a toxic range.In urethane anesthetized mechanically ventilated rats, NaHS was intravenously infused in a stepwise manner to produce an increase in alveolar H2S partial pressure and thus arterial concentration of free H2S (CgH2S) from undetectable up to levels we have previously shown to depress breathing control.Compared to saline infusion, blood pressure started to decrease significantly along with the peripheral vascular resistance by ‐19 ± 5%, (P<0.01) when CgH2S reached ~ 1 microM. As soon as CgH2S exceeded these levels, cardiac output decreased with a decrease in ventricular pressure, along with a significant elevation of blood lactate. Whenever H2S exposure was maintained at a higher level, above 3‐4 microM of CgH2S, a profound inhibition of cardiac contractility occurred leading to cardiac arrest by a pulseless electrical activity.In conclusion, a small reduction in peripheral vascular resistance was found in the rat at relatively low H2S concentrations. These changes were extremely modest with an alarming overlap with the levels of H2S altering cardiac contractility.