Arterial Pressure Responses Research Articles

Abstract P305: Sympathetic Activation Elicited by Bilateral Carotid Occlusion Attenuates Cytokine Release in Conscious Endotoxemic Rats

Our previous studies suggest that carotid occlusion can induce a sympathetic signal able to modulate the immune system. Here, we analyze whether bilateral carotid occlusion (BCO) affect the innate immune response to bacterial lipopolysaccharide (LPS) in endotoxic rats. In order to prevent the neuronal alterations induced by anesthesia, we performed our studies of BCO in conscious rats. Wistar rats were implanted with pneumatic cuffs around the common carotid arteries for BCO. Femoral and peritoneal catheters were also inserted for blood pressure recording and LPS administration. Rats were randomly assigned to the following groups: Saline, LPS + SHAM (LPS in the presence of the occluders but without occlusion) and LPS + BCO (LPS combined with bilateral carotid occlusion). BCO was performed for 20s in conscious awake rats, right before LPS (5.0 mg/kg) or saline (control) administration. Plasma and spleen samples were collected at 90 min after LPS or saline administration. As compared to baseline arterial pressure, BCO produced a peak response in mean arterial pressure of 52 ± 3 mmHg, confirming the sympathetic activation. BCO significantly attenuated TNF-α and IL-1β plasma levels as compared to those in SHAM endotoxemic rats [TNF: 1319 ± 388 (n = 6) vs. 583 ± 138 pg/mL (n = 8), P = 0.03; IL-1β: 2203 ± 256 (n = 5) vs. 1086 ± 157 pg/mL (n = 9), P < 0.001]. BCO also significantly reduced the TNF-α levels in the spleen [5.1 ± 1.3 (n = 7) vs. 1.7 ± 0.4 pg/mg tissue (n = 8), P = 0.005]. By contrast, BCO did not significantly change IL-6 and IL-10 levels in plasma [IL-6: 5609 ± 352 (n = 7) vs. 5879 ± 375 pg/mL (n = 10), P = 0.703; IL-10: 2417 ± 354 (n = 5) vs. 2068 ± 298 pg/mL (n = 9), P = 0.408] or in the spleen [IL-6: 15 ± 3 (n = 7) vs. 14 ± 2 pg/mg tissue (n = 10) P = 0.776; IL-10: 1.6 ± 0.2 (n = 7) vs. 1.3 ± 0.2 pg/mg tissue (n = 9), P = 0.475]. Moreover, the IL-1β level in the spleen was not affected by BCO [54 ± 12 (n = 6) vs. 28 ± 5 pg/mg tissue (n = 9), P = 0.058]. These findings indicate that sympathetic activation by BCO in conscious rats attenuates the pro-inflammatory cytokines release in the endotoxemic model induced by LPS without affecting anti-inflammatory cytokine IL-10.

Arterial blood pressure responses to short-term exposure to fine and ultrafine particles from indoor sources – a randomized sham-controlled exposure study

Arterial blood pressure responses to short-term exposure to fine and ultrafine particles from indoor sources – a randomized sham-controlled exposure study

C-Jun N-terminal Kinase mediates prostaglandin-induced sympathoexcitation in rats with chronic heart failure by reducing GAD1 and GABRA1 expression.

Prostaglandin E2 mediates sympathoexcitation in chronic heart failure (CHF) through EP3 receptors (PTGER3) in the paraventricular nucleus (PVN). The aim of this study was to investigate the role of c-Jun N-terminal kinase (JNK) in expressional regulation of gamma-aminobutyric acid signalling in PVN in CHF rats. Chronic heart failure was induced by left coronary ligation in Wistar rats. Renal sympathetic nerve discharge (RSND) and mean arterial pressure (MAP) responses to the PVN infusion were determined in anaesthetized rats. Osmotic minipumps were used for chronic PVN infusion. PTGER3 expression was examined with immunofluorescence staining, quantitative real-time PCR and Western blot. Chronic heart failure rats had increased JNK activation and decreased glutamate decarboxylase 1 (GAD1) and GABAA receptor alpha 1 subunit (GABRA1) expression in the PVN. PVN infusion of the PTGER3 agonist SC-46275 caused sympathoexcitation in sham-operated control (Sham) rats and increased it further in CHF. The PTGER3 antagonist L798106 reduced sympathoexcitation and cardiac dysfunction in CHF. PVN infusion of EP1 receptor antagonist SC-19220, EP2 receptor antagonist AH6809 or EP4 receptor antagonist L-161982 had no effect on sympathoexcitation. The JNK inhibitor SP600125 normalized sympathoexcitation and GAD1 and GABRA1 expression in PVN in CHF rats. Both the p44/42 and p38 mitogen-activated protein kinase inhibitors PD98059 and SB203580 could not prevent the downregulation of GAD1 and GABRA1 expression in PVN in CHF. PTGER3 agonist activated JNK but downregulated GAD1 and GABRA1 expression in NG108 neuronal cells. Prostaglandin signalling through upregulated PTGER3 activates JNK which reduces GAD1 and GABRA1 expression in the PVN, and contributes to sympathoexcitation in CHF.

Short-Term Angiotensin Subtype 1 Receptor Blockade Does Not Alter the Circulatory Responses to Sympathetic Nervous System Modulation in Healthy Volunteers Before and During Sevoflurane Anesthesia: Results of a Pilot Study

The mechanism of perioperative hypotension in patients taking an angiotensin-receptor blocker up to the time of surgery remains unclear. This study tested the hypothesis that short-term angiotensin-receptor blocker treatment attenuated the sympathetic and vascular responses to autonomic stimuli in volunteers undergoing anesthesia. Randomized, crossover, blinded, pilot design. Zablocki Veterans Affairs Medical Center, Milwaukee, WI. The study comprised 8 male and 6 female healthy, young volunteers (age 23±1.2 years [mean±standard error of the mean]). Volunteers were studied after receiving oral placebo or 50 mg of losartan (angiotensin-receptor blocker) for 3 days before each test day. The effectiveness of angiotensin-receptor blocker treatment was confirmed using the mean arterial blood pressure response to intravenous angiotensin II (1-µg bolus). Eight volunteers underwent direct mean arterial pressure and forearm bloodflow measurements during conscious baseline, a cold pressor test, induction of anesthesia, tracheal intubation, maintenance of anesthesia with 1 minimum alveolar concentration of sevoflurane, and airway irritation with 12% desflurane. Six volunteers experienced mean arterial pressure responses to 0.1 mg of phenylephrine at baseline and during 1 minimum alveolar concentration of sevoflurane. Comparisons were made over time and across groups. Angiotensin-receptor blocker treatment significantly reduced-mean arterial pressure and forearm vascular resistance (forearm blood flow/mean arterial pressure) over time and blocked the mean arterial pressure response to angiotensin-II challenge. The changes in mean arterial pressure and forearm vascular resistance in response to all stressors did not differ between treatments. Mean arterial pressure increases from phenylephrine were preserved. In healthy, young volunteers, sympathetically-mediated responses from the short-term use of an angiotensin-receptor blocker were not altered and most likely did not contribute to perioperative hypotension during the intraoperative period.

Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response.

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g−1 FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g−1 FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g−1 FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia.

A novel intravenous vehicle for preclinical cardiovascular screening of small molecule drug candidates in rat

Screening novel, poorly soluble small-molecule candidates for cardiovascular liabilities represents a key challenge in early drug discovery. This report describes a novel vehicle composed of 20% N,N-Dimethylacetamide (DMA)/40% Propylene glycol (PG)/40% Polyethylene Glycol (PEG-400) (DPP) for administration of new chemical entities (NCEs) by slow intravenous (i.v.) infusion in a preclinical anesthetized rat model. The vehicle was designed considering both available excipient safety information and solubilization potential for poorly soluble NCEs. DPP solubilized 11 drugs, 8 of which were insoluble in 5% dextrose in water (D5W), and 5 insoluble in PEG-400 to a target concentration of 30mg/mL. DPP elicits no adverse cardiovascular responses in the anesthetized rat model despite containing 40% PEG-400, a commonly used organic solvent which elicits hypertension and bradycardia that often confounds interpretation of drug effects. Three compounds demonstrating adequate solubility in both DPP and D5W were screened in the anesthetized rat model. When normalized to plasma exposure, atenolol, sotalol and enalaprilat exhibited comparable mean arterial pressure, heart rate, and cardiac contractility responses regardless of formulation. While the antihypertensive effect of nifedipine was evident with both DPP and PEG-400 formulations, pressor effects from PEG-400 confounded interpretation of the magnitude of nifedipine's response. Plasma concentrations of atenolol and enalaprilat were greater in D5W formulation whereas sotalol exposures were greater when using DPP as a vehicle. These results demonstrate the utility of DPP as an intravenous vehicle for formulating poorly soluble compounds in early preclinical screening for cardiovascular safety studies.

Responses of Endothelin-1 and Arterial Blood Pressure of Postmenopausal Women to Aerobic Exercise Training

Responses of Endothelin-1 and Arterial Blood Pressure of Postmenopausal Women to Aerobic Exercise Training

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension.

Effects of intravenous and topical laryngeal lidocaine on heart rate, mean arterial pressure and cough response to endotracheal intubation in dogs

ObjectiveTo compare the effects of intravenous (IV) and topical laryngeal lidocaine on heart rate (HR), mean arterial pressure (MAP) and cough response to endotracheal intubation (ETI) in dogs. Study designProspective, randomized, blinded clinical study. AnimalsForty-two client-owned dogs (American Society of Anesthesiologists class I and II status) undergoing elective orthopaedic surgery. MethodsDogs were randomized to three groups. Dogs in group SALIV received 0.1 mL kg−1 IV saline. Dogs in group LIDIV received 2 mg kg−1 IV 2% lidocaine. Dogs in group LIDTA received 0.4 mg kg−1 topically sprayed laryngeal 2% lidocaine. All dogs were premedicated with methadone (0.2 mg kg−1 IV). After 30 minutes, IV propofol was administered to abolish the lateral palpebral reflex and produce jaw relaxation. The allocated treatment was then administered and, after 30 seconds, further propofol was administered to abolish the medial palpebral reflex and facilitate ETI. HR and MAP were measured at four time-points using cardiac auscultation and automated oscillometry, respectively. The cough response at ETI was recorded. One-way anova and post hoc Tukey adjustment were used to analyse parametric data. The Kruskal-Wallis test was used to analyse non-parametric data. Odds ratios were calculated for the cough response. A p-value of =0.05 was considered to indicate statistical significance. ResultsIn response to ETI, changes in MAP differed significantly between groups. In SALIV, MAP increased (4 ± 6 mmHg), whereas it decreased in LIDIV (6 ± 13 mmHg) (p= 0.013) and LIDTA (7 ± 11 mmHg) (p= 0.003). Dogs in SALIV were almost 10 times more likely to cough than dogs in LIDIV (odds ratio 9.75, 95% confidence interval 0.98–96.60; p = 0.05). Conclusions and clinical relevanceIn propofol-anaesthetized dogs, IV and topical laryngeal lidocaine attenuated the pressor response to ETI, whereas IV lidocaine reduced the cough response.

Effect of Algerian Varieties Dates on Glycemic, Arterial Blood Pressure and Satiety Responses

The purpose of our study is to determine the Glycemic Indexes (GIs) of three Algerians varieties of dates in healthy subjects evaluate the satiety and effect on arterial pressure after their consumption. We have first documented the chemical composition of the dates. 10 healthy subjects consumed the dates (carbohydrates content of 50 g) in order to determine the GIs. The responses of glycaemia were monitored during two hours after the dates taking and compared to the reference glucose. In a randomized trial, 20 healthy adults consumed the dates after 12h of fast. We reported the level of satiety on a Visual Analog Scale for 2h further to the ingestion of the dates. Furthermore, 28 normotensives and 45 hypertensive individuals ingested the three varieties in randomized order during 21 days to assess their impact on the Pressure Arterial Systolic (PAS) and Pressure Arterial Diastolic (PAD). We noted significant differences (p<0.05) for the different fractions of sugars, soluble fibers, polyphenols, K<sup>+</sup>, Mg<sup>2+</sup>. The low GIs are denoted among 44.31-52.35, deducting a moderate impact on blood glucose level. The dates reduced hunger and increased satiety. Our varieties studied following their ingestion induced a significant hypotensive activity (p<0.05) on the PAS and, PAD from hypertensive subjects.

Influence of prior hyperventilation duration on respiratory chemosensitivity and cerebrovascular reactivity during modified hyperoxic rebreathing

What is the central question of this study? We characterized and compared the cardiorespiratory and cerebrovascular responses to the 'Duffin' modified hyperoxic CO2 rebreathing test by randomly altering the prior hyperventilation duration. What is the main finding and its importance? Our main finding was that prior hyperventilation duration (1, 3 or 5min) had no effect on cardiorespiratory and cerebrovascular responses to the hyperoxic rebreathing test, within individuals. These findings suggest that the standard 5min prior hyperventilation duration used to clear body CO2 stores is unnecessary and can reasonably be shortened to 1min, reducing protocol times and improving participant comfort. The 'Duffin' modified hyperoxic rebreathing test allows investigators to characterize and quantify the ventilatory and cerebrovascular responses to CO2 across a large physiological range, allowing quantification of basal ventilation and the ventilatory recruitment threshold (VRT). Although the standard protocol includes 5min of prior hyperventilation to clear body CO2 stores, there is no experimental evidence that a full 5min is required. We hypothesized that there would be no within-individual differences in the cardiorespiratory or cerebrovascular responses to rebreathing with shortened hyperventilation duration prior to hyperoxic rebreathing. Using a rebreathing apparatus, transcranial Doppler ultrasound and beat-to-beat blood pressure monitoring, we tested 19 participants in the supine position using three randomly assigned hyperoxic rebreathing tests with 1, 3 or 5min of prior hyperventilation. We measured VRT (in Torr CO2 ), time to VRT (in seconds), central respiratory chemoreflex (breathing frequency, tidal volume and minute ventilation), cerebrovascular (middle and posterior cerebral artery velocity) and cardiovascular (heart rate and mean arterial pressure) responses to CO2 during hyperoxic rebreathing. Using linear regression and repeated-measures ANOVAs, we found no differences in any of the cardiorespiratory or cerebrovascular response magnitudes between trials (P>0.05). The only difference observed was in the time to VRT (in seconds), whereby 1min prior hyperventilation duration was shorter (135.4±19.7s) than with 3 or 5min prior hyperventilation (176.3±15.1 and 187.2±11.6s, respectively; P<0.001). Our findings indicate that 5min of prior hyperventilation is unnecessary during modified rebreathing when using it to quantify respiratory or cerebrovascular responses and can be reasonably shortened to 1min, reducing protocol times and improving participant comfort.

Central leptin and resistin combined elicit enhanced central effects on renal sympathetic nerve activity.

What is the central question of this study? Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. We also used Fos protein to quantify the number of activated neurons in the brain. What is the main finding and its importance? A combination of leptin and resistin induced a greater increase in RSNA than either hormone alone. This was correlated with a greater number of activated neurons in the arcuate nucleus than with either hormone alone. Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. Mean arterial pressure, heart rate and RSNA were recorded before and for 3h after intracerebroventricular saline (control; n=5), leptin (7μg; n=5), resistin (7μg; n=4) and leptin administered 15min after resistin (n=6). Leptin alone and resistin alone significantly increased RSNA (74±17 and 50±14%, respectively; P<0.0001 compared with saline). When leptin and resistin were combined, there was a significantly greater increase in RSNA (163±23%) compared with either hormone alone (P<0.0001). Maximal responses of mean arterial pressure and heart rate were not significantly different between groups. We also used Fos protein to quantify the number of activated neurons in the brain. Compared with controls, there were significant increases in numbers of Fos-positive neurons in the arcuate and hypothalamic paraventricular nuclei when leptin or resistin was administered alone or when they were combined, and in the lamina terminalis when leptin and resistin were combined. Only in the arcuate nucleus was the increase significantly greater compared with either hormone alone. The findings show that a combination of leptin and resistin induces a greater RSNA increase and a greater number of activated neurons in the arcuate nucleus than with either hormone alone. Given that leptin makes an important contribution to the elevated RSNA observed in obese and overweight conditions, the increased concentrations of leptin and resistin may mean that the contribution of leptin to the elevated RSNA in those conditions is enhanced.

Sensitivity of the Vascular Response Range in Determining Aerobic Fitness

Previous work demonstrates a direct relationship between aerobic fitness and vasodilatory function (i.e., Flow-mediated Dilation; FMD). Recent evidence suggests that artery vasoconstrictor responses to reductions in blood flow (Low-Flow Mediated Constriction; LFMC) may compliment FMD, and provide an overall range of vascular responsiveness. PURPOSE: To test the hypothesis that the vascular response range (VRR=FMD+LFMC) is sensitive to differences in aerobic fitness. METHODS: Fourteen healthy males (age: 22±4 yrs) were recruited, and divided evenly into a high (HF) vs. low (LF) aerobic fitness group, quantified via YMCA cycle ergometry (VO2 peak extrapolation), and a 3-min step test (1-min HR recovery). Doppler-ultrasound was used to assess brachial artery VRR. In brief, artery diameter and flow velocity signals were obtained simultaneously for 2 mins prior to, 30 sec during, and for 3 mins following release of a distally placed occlusion cuff (220 mmHg, for 5 mins). FMD was calculated as the peak change in artery diameter following cuff-release, and LFMC was calculated from the nadir diameter obtained during the 30 sec prior to cuff-release. RESULTS: VO2 peak (HF=55±10 vs. LF=38±6; P<0.01) and HR recovery (HF=38±12 vs. LF=24±9 beats; P<0.05) were greater in the HF group. VRR and FMD% were similar between groups; however, LFMC tended to be greater in HF (HF=-0.1±0.06 vs. LF=-0.02±0.07mm, P=0.055). A correlational analysis revealed an inverse relation between LFMC (%) and HR recovery (r=-0.631, P=0.016). Finally, the resting diameter (mm) calculated as a percentage of VRR (i.e., %-tone) tended to be greater in LF (HF=72±17 vs. 96±25%, P=0.055). CONCLUSION: These preliminary findings suggests that brachial VRR is not sensitive to aerobic fitness in healthy young men; however, high fit individuals may exhibit less tone, and greater vasoconstrictor responses to reductions in blood flow.

Generalized Response of the Exercise Pressor Reflex

Autonomic responsiveness to reflex stimuli varies considerably between individuals, with implications for predicting cardiovascular disease. PURPOSE: To standardize blood pressures to activation of the exercise pressor reflex using isometric handgrip exercise followed by post-exercise circulatory arrest (PECA). METHODS: Using specific search terms including “metaboreflex”, “ergoreflex”, “handgrip”, “reflex”, “static”, and “isometric”, we identified 151 studies that quantified the pressor response to handgrip exercise followed by PECA in healthy humans aged 19-44 years. We characterized these studies by exercise mode (static vs. dynamic), percentage of maximum voluntary contraction, blood pressure measurement technique, duration of exercise, duration of PECA, and method of data presentation (absolute values vs. changes from baseline). Preliminary analysis revealed distinct effects of exercise intensity and duration. We constrained further analysis to studies including healthy adults completing isometric handgrip exercise at 30-33% of maximum for 3 minutes and 2 or more minutes of PECA, with blood pressure measured from the wrist or finger of the resting arm (total of 4 studies). RESULTS: Using the reported means and variation we employed bootstrapping with weighted re-sampling (n=10,000) to create a statistically comparable normal distribution of responses. Based on these criteria, the average population mean arterial pressure response for the second minute of PECA is 19 mmHg. The first quartile response is 13 mmHg, and the third quartile is 26 mmHg. CONCLUSIONS: The autonomic response following ischemic handgrip varies considerably between individuals, even when experimental conditions are standardized. The possible foundation for these differences may be neural (e.g., afferent, central, or efferent) or extra-neural (e.g., genetic, muscle fiber type, or vascular).

Artificial reproduction of magnetic fields produced by a natural geomagnetic storm increases systolic blood pressure in rats.

The incidence of geomagnetic storms may be associated with changes in circulatory physiology. The way in which the natural variations of the geomagnetic field due to solar activity affects the blood pressure are poorly understood and require further study in controlled experimental designs in animal models. In the present study, we tested whether the systolic arterial pressure (AP) in adult rats is affected by simulated magnetic fields resembling the natural changes of a geomagnetic storm. We exposed adult rats to a linear magnetic profile that simulates the average changes associated to some well-known geomagnetic storm phases: the sudden commencement and principal phase. Magnetic stimulus was provided by a coil inductor and regulated by a microcontroller. The experiments were conducted in the electromagnetically isolated environment of a semi-anechoic chamber. After exposure, AP was determined with a non-invasive method through the pulse on the rat's tail. Animals were used as their own control. Our results indicate that there was no statistically significant effect in AP when the artificial profile was applied, neither in the sudden commencement nor in the principal phases. However, during the experimental period, a natural geomagnetic storm occurred, and we did observe statistically significant AP increase during the sudden commencement phase. Furthermore, when this storm phase was artificially replicated with a non-linear profile, we noticed a 7 to 9% increase of the rats' AP in relation to a reference value. We suggested that the changes in the geomagnetic field associated with a geomagnetic storm in its first day could produce a measurable and reproducible physiological response in AP.

Arterial blood pressure and heart rate response in patients with acute ischemic stroke - Correlation with the severity of cardiovascular autonomic dysfunction

Background and purpose: Despite numerous studies, the mechanisms of blood pressure and heart rate regulation in cerebrovascular diseases remain not completely understood. The aim of the study was to determine the changes in blood pressure (BP) and heart rate (HR) in patients with an acute hemispheric ischemic stroke and to seek a relation to the severity of the cardiovascular autonomic dysfunction. Methods: 20 healthy volunteers and 50 patients with an acute hemispheric ischemic stroke participated in the study. The values of BP and HR were registered. Cardiovascular autonomous disorders were examined with Ewing battery tests. Patients were divided into two groups according to the severity of the autonomous disorders. Results: Elevated BP values at admission were observed in 56% of our patients, and significantly higher values of systolic blood pressure (SBP) (p <0,001), diastolic blood pressure (DBP) (p = 0,001), and mean arterial pressure (p <0,001), as well as of the heart rate (p = 0,027) were found, compared to the control group. The most significantly increased values of the indicators were reported in patients with a stroke in the territory of the right middle cerebral artery with an involvement of the insular cortex. The results of the t-test performed, showed correlation only between the systolic blood pressure and the severity of the autonomic dysfunction, the values being significantly higher in patients with severe autonomic disorders (t = -2,14; p = 0.036). Conclusion: A variability in BP and HR with a tendency to increase was observed in patients with an acute hemispheric ischemic stroke (ICS) compared to controls, with the highest values reported in patients with ICS in the territory of right middle cerebral artery (TRMCA) with the involvement of the insular cortex (IC). A positive correlation was found between the values of systolic blood pressure (SBP) and the severity of autonomic dysfunction (AD).

The arterial baroreflex and inherent G tolerance.

High G tolerance is based on the capacity to maintain a sufficient level of arterial pressure (AP) during G load; therefore, we hypothesized that subjects with high G tolerance (H group) would have stronger arterial baroreflex responses compared to subjects with low G tolerance (L group). The carotid baroreflex was evaluated using the neck pressure method (NP), which assesses open-loop responses. The carotid baroreflex was tested in 16 subjects, n=8 in the H and L group, respectively, in the supine and upright posture. Heart rate and AP were measured. There were no differences between groups in the maximum slopes of the carotid baroreflex curves. However, the H group had a larger systolic and mean AP (SAP, MAP) increase to the initial hypotensive stimuli of the NP sequence in the upright position compared to the L group, 7.5±6.6 vs 2.0±2.4 and 4.1±3.4 vs 1.1±1.1mmHg for SAP and MAP, respectively. Furthermore, the L group exhibited an increased latency between stimuli and response in AP in the upright compared to supine position, 4.1±1.0 vs 3.1±0.9 and 4.7±1.1 vs 3.6±0.9s, for SAP and MAP. No differences in chronotropic responses were observed between the groups. It is concluded that the capacity for reflexive vasoconstriction and maintained speed of the vascular baroreflex during orthostatic stress are coupled to a higher relaxed GOR tolerance.

Blunted Arterial Blood Pressure Responses to Whole‐Body Cold Stress in Individuals with Multiple Sclerosis

Multiple sclerosis (MS) is a neurological disease in which demyelination disrupts signal transmission and/or integration within the central nervous system. Reduced resting MSNA has been previously reported in MS patients (Keller et al., 2014). The aim of this study was to test the hypothesis that individuals with MS will have blunted sympathetic‐mediated responses to a whole‐body cold stress stimulus compared to healthy controls (CON). Ten subjects with relapsing‐remitting MS (age, 35±7 years old; height: 163±9 cm; weight: 64±12 kg; BSA: 1.7±0.2 m2) and 4 healthy controls (31±5 years old; height: 168±6 cm; weight: 66±14 kg; BSA: 1.7±0.2 m2) participated in the study. Subjects were instrumented with a tube‐lined water perfusion suit in which they were exposed to a thermoneutral (34 °C circulating water) condition for a baseline period of 10 minutes, followed by a 3‐minute whole‐body cold stress (5 °C circulating water) condition. Skin blood flow (laser‐Doppler flowmetry), beat‐to‐beat arterial pressure (photoplethysmography), heart rate (ECG), and mean skin temperature were continuously measured. Cutaneous vascular conductance was calculated from the ratio of laser‐Doppler flux to mean arterial pressure (CVC) and normalized to maximal responses obtained by local heating at 42 °C following cooling (%CVCmax). Mean arterial pressures (MAP) were derived during the final minute of baseline and cooling. There were no differences in ΔLDF flux (CON: −2.83±3.76; MS: −3.73±4.29, p=0.72), ΔCVC (CON: −0.05± 0.06; MS: −0.05±0.06, p=0.89), and Δ%CVCmax (CON: −2.43±3.75; MS: −0.24, p=0.12) from baseline to cooling. However, there was a significant difference in ΔMAP between groups (CON: 12.17±9.70; MS: −0.99±7.00, p=0.01). While cutaneous vasoconstrictor responsiveness was similar between groups, these data suggest individuals with MS exhibit reduced sympathetic‐mediated changes in blood pressure in response to a whole body cold stress.Support or Funding InformationProject funded by NIH grant (R15 HL117224) and National Multiple Sclerosis Society grants (RG4043A and RG4696A)

Upregulation of Orexin in the Paraventricular Nucleus Contributes to Salt Sensitive Hypertension

Orexin and orexin receptors are extensively expressed in the hypothalamic paraventricular nucleus (PVN) and the hyperactivity of PVN orexin contributes to increased sympathetic nerve activity (SNA) and elevated blood pressure in several animal models. However, the role of PVN orexin in the development of salt sensitive hypertension (SSHTN) is unknown. In this study, we tested the hypothesis that PVN orexin expression is increased in SSHTN and contributes to the development of SSHTN via regulating vasopressin secretion. Eight‐week‐old Dahl salt sensitive (DS) rats were divided into two groups and were fed either a high salt (HS, 8% NaCl) or normal salt (NS, 0.4% NaCl) diet. Six weeks following diet treatment, rats were anesthetized and their mean arterial pressure (MAP) and sympathetic nerve activity (SNA) response to orexin receptor blockade were recorded. In a separate group of rats PVN orexin mRNA levels were measured. The results showed that HS intake induced significant increases in MAP (HS: 146±2 vs. NS: 112±5; n=5; P&lt;0.05) and PVN orexin mRNA levels (HS: 3.8±0.37 vs. NS: 1.0±0.68; n=3; P&lt;0.05). Bilateral PVN microinjection of orexin receptor 1 (OX1R) antagonist SB408124 (30 pmol/50nl) resulted in a greater reduction in arterial blood pressure in DS rats with a HS intake compared to their cohorts with a NS diet (HS: −16±5 vs. NS: −4±4 mmHg; n=5–6; P&lt;0.05). OX1R blockade also increased splanchnic SNA (HS: 48.2±12.6%) vs. NS: 35.82±9%; P=0.2) and renal SNA (HS: 26.7±7.5% vs. NS: 17.4±9.5%; P=0.2) in DS rats with either HS or NS diet. Incubation of orexin A resulted in a dose‐dependent increase in vasopressin mRNA levels (100nM: 2.9‐fold; 1μM; 5.6 fold; 10μM: 18‐fold) in primary cultured neurons from the hypothalamus containing the PVN of neonatal Sprague Dawley rats. These orexin A‐induced increases of vasopressin mRNA were abolished by OX1R blockade. These results coupled with the evidence that plasma vasopressin is upregulated in DS rats under the condition of HS‐induced hypertension suggest that increased PVN orexin expression may be involved in the development of SSHTN through regulating vasopressin secretion.Support or Funding InformationThis study is supported by AHA 11SDG7420029 and NIH R15‐HL122952.

Predicting muscle sympathetic nerve activity and mean arterial blood pressure responses to mental stress

Mental stress consistently increases mean arterial pressure (MAP), but changes in muscle sympathetic nerve activity (MSNA) during mental stress can vary widely between subjects. The MAP responsiveness to mental stress has been reported to be augmented in both prehypertensive and obese adults when compared to normotensive and normal weight adults, respectively. Cardiovascular reactivity to mental stress has been suggested as a predictor of hypertensive risk (i.e., cardiovascular reactivity hypothesis), yet the major contributing factors to the MSNA and MAP responses to mental stress remain unclear. Predictive independent variables include factors such as resting blood pressure, sex, and body mass index (BMI). Therefore, we used a regression selection method with an algorithm that employed both forward selection and backward elimination to determine the best explanatory variable for the changes in MSNA (ΔMSNA) and MAP (ΔMAP) during mental stress. Predictive independent variables included resting systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), mean arterial blood pressure (MAP), heart rate, sex, age, and BMI in 97 adults (67 males and 30 females). Heart rate, MSNA, and MAP were simultaneously and continuously recorded during a 5–10 min supine baseline and 5 min of mental stress (via mental arithmetic). The strongest predicting variable for ΔMSNA responses to mental stress was BMI (p&lt;0.02), which explained 3.5% of the variance; BMI and ΔMSNA were significantly correlated (p&lt;0.04). In contrast, the strongest predicting variable for ΔMAP responses to mental stress was resting SAP (p&lt;0.02), which explained 5.6% of the variance; resting SAP and ΔMAP responses to mental stress were significantly correlated (p&lt;0.01). We conclude that BMI is the predominant factor that contributes to the ΔMSNA response to mental stress, while resting SAP is the most important contributing factor to ΔMAP responses. Our findings reinforce the importance of both BMI and resting blood pressure in neural cardiovascular reactivity studies.Support or Funding InformationThis project was supported by a Michigan Technological University Research Excellence Fund Seed Grant to J. Durocher.