Endogenous substance P modulates human cardiovascular regulation at rest and during orthostatic load

2007 ◽  
Vol 102 (6) ◽  
pp. 2092-2097 ◽  
Author(s):  
Matthew V. Dzurik ◽  
André Diedrich ◽  
Bonnie Black ◽  
Sachin Y. Paranjape ◽  
Satish R. Raj ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Substance P ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Muscle Sympathetic Nerve Activity ◽  
Cardiovascular Regulation ◽  
Postural Adjustment ◽  
Compensatory Mechanisms ◽  
Double Blind

Substance P (SP) is a peptide neurotransmitter identified in many central and peripheral neural pathways. Its precise role in human physiology has been difficult to elucidate. We used the selective neurokinin 1 (NK1) antagonist aprepitant as a pharmacological probe to determine the role of endogenous SP in human cardiovascular regulation. We performed a randomized, double-blind, placebo-controlled, crossover trial in healthy subjects. Blockade of endogenous NK1 receptors reduced resting muscle sympathetic activity 38% ( P = 0.002), reduced systemic vascular resistance by 25% ( P = 0.021), and increased cardiac index by 47% ( P = 0.006). This constellation of changes did not, however, alter either blood pressure or heart rate in the supine position. NK1 antagonism also raised orthostatic heart rate change by 38% ( P = 0.023), although during the incremental postural adjustment on the tilt table neither heart rate nor blood pressure was altered significantly. Despite a mildly attenuated vagal baroreflex with SP blockade, the depressor and pressor responses to nitroprusside and phenylephrine did not differ compared with placebo, suggesting other compensatory mechanisms. NK1 blockade manifests as a decrease in muscle sympathetic nerve activity and systemic vascular resistance. Our study suggests SP exerts a tonic enhancement of sympathetic outflow to some cardiovascular structures via its modulation of the NK1 receptor. Most likely, this ubiquitous neurotransmitter exerts effects at multiple sites that, in the aggregate, are relatively well compensated under many circumstances but may emerge with perturbations. This study is consistent with a role for SP afferents in supporting peripheral vascular resistance.

Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Cognitive Functions ◽  
Cardiovascular Regulation ◽  
Double Blind ◽  
Positive Effects ◽  
Pressure Tests ◽  
Healthy Males

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

scholarly journals Disturbed Cardiorespiratory Adaptation in Preeclampsia: Return to Normal Stress Regulation Shortly after Delivery?

2019 ◽  
Vol 20 (13) ◽  
pp. 3149 ◽  
Author(s):  
Lackner ◽  
Papousek ◽  
Schmid-Zalaudek ◽  
Cervar-Zivkovic ◽  
Kolovetsiou-Kreiner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Physiological Stress ◽  
Cardiovascular Responses ◽  
Stressful Events ◽  
Severe Preeclampsia ◽  
Stroke Index ◽  
Increased Risk

Women with pregnancies complicated by preeclampsia appear to be at increased risk of metabolic and vascular diseases in later life. Previous research has also indicated disturbed cardiorespiratory adaptation during pregnancy. The aim of this study was to follow up on the physiological stress response in preeclampsia several weeks postpartum. A standardized laboratory test was used to illustrate potential deviations in the physiological stress responding to mildly stressful events of the kind and intensity in which they regularly occur in further everyday life after pregnancy. Fifteen to seventeen weeks postpartum, 35 women previously affected by preeclampsia (19 mild, 16 severe preeclampsia), 38 women after uncomplicated pregnancies, and 51 age-matched healthy controls were exposed to a self-relevant stressor in a standardized stress-reactivity protocol. Reactivity of blood pressure, heart rate, stroke index, and systemic vascular resistance index as well as baroreceptor sensitivity were analyzed. In addition, the mutual adjustment of blood pressure, heart rate, and respiration, partitioned for influences of the sympathetic and the parasympathetic branches of the autonomic nervous system, were quantified by determining their phase synchronization. Findings indicated moderately elevated blood pressure levels in the nonpathological range, reduced stroke volume, and elevated systemic vascular resistance in women previously affected by preeclampsia. Despite these moderate abnormalities, at the time of testing, women with previous preeclampsia did not differ from the other groups in their physiological response patterns to acute stress. Furthermore, no differences between early, preterm, and term preeclampsia or mild and severe preeclampsia were observed at the time of testing. The findings suggest that the overall cardiovascular responses to moderate stressors return to normal in women who experience a pregnancy with preeclampsia a few weeks after delivery, while the operating point of the arterial baroreflex is readjusted to a higher pressure. Yet, their regulation mechanisms may remain different.

Haemodynamic and Neurohumoral Effects of Caffeine in Elderly Patients with Symptomatic Postprandial Hypotension: A Double-Blind, Randomized, Placebo-Controlled Study

1994 ◽  
Vol 87 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Lewis A. Lipsitz ◽  
Rene W. M. M. Jansen ◽  
Carolyn M. Connelly ◽  
Margaret M. Kelley-Gagnon ◽  
Anthony J. Parker
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Elderly Patients ◽  
Blood Volume ◽  
Vascular Resistance ◽  
Controlled Study ◽  
Pathophysiological Mechanism ◽  
Double Blind ◽  
Postprandial Hypotension ◽  
Forearm Vascular Resistance

1. The aim of this study was to determine the effects of caffeine on haemodynamic and neurohumoral responses to meal ingestion in elderly patients with a history of symptomatic postprandial hypotension. 2. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly, associated with falls and syncope. The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal. Since caffeine inhibits vasodilatory adenosine receptors in the splanchnic circulation, we postulated that caffeine would reduce splanchnic blood pooling and prevent the development of postprandial hypotension. 3. We conducted a randomized, double-blind, placebo-controlled, cross-over study in nine elderly patients [age 76 ± 9 (SD) years] with histories of symptomatic postprandial hypotension. Standardized 1674 kJ liquid meals with 250 mg of caffeine or placebo were given on two occasions, at least 1 week apart. Blood pressure, heart rate, forearm vascular resistance (by venous occlusion plethysmography), and plasma caffeine and catecholamine levels were measured. Cardiac and splanchnic blood volume were determined by radionuclide scans. 4. By 30 min after both caffeine and placebo meal studies, supine mean arterial blood pressure fell significantly (P = 0.006) by 31 ± 7 and 19 ± 6 mmHg, respectively (mean ± SEM, between group difference was not significant). Heart rate, cardiac output and splanchnic blood volume increased significantly, but to a similar extent, after caffeine and placebo. Forearm vascular resistance was unchanged after both meals. 5. Oral caffeine given with a meal does not reduce splanchnic blood pooling nor prevent postprandial hypotension in symptomatic elderly patients.

scholarly journals Blood pressure control during exercise in the Atlantic cod, Gadus morhua

1986 ◽  
Vol 126 (1) ◽  
pp. 225-236 ◽  
Author(s):  
M. Axelsson ◽  
S. Nilsson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Atlantic Cod ◽  
Plasma Concentrations ◽  
Blood Samples ◽  
Blood Pressures ◽  
Mixed Venous

Atlantic cod were subjected to 12–15 min swimming exercise at 2/3 body lengths s-1 in a Blazka-type swim tunnel. Pre- and postbranchial blood pressures, cardiac output (ventral aortic blood flow) and heart rate were continuously recorded, and blood samples for measurement of arterial and mixed venous oxygen tension were taken before and at the end of the exercise period. In a second group of fish, subjected to similar exercise regimes, blood samples were taken for analysis of the plasma concentrations of catecholamines. Pre- and postbranchial blood pressures and cardiac output increase during exercise, while the mixed venous oxygen tension decreases. The effect on cardiac output is due to an increase of both heart rate and stroke volume. There are no significant changes in either systemic or branchial vascular resistances, or in the plasma concentrations of catecholamines. Injection of the adrenergic neurone-blocking drug bretylium produces a decrease in postbranchial blood pressure in resting cod, due to a decrease in the systemic vascular resistance. Exercising cod treated with bretylium have a significantly lower pre- and postbranchial blood pressure than exercising control cod. This is due mainly to a dramatic reduction in the systemic vascular resistance. The alpha-adrenoceptor antagonist phentolamine does not further affect the blood pressure in cod treated with bretylium. It is concluded that the exercise hypertension observed in cod depends on the effect of adrenergic vasomotor fibres maintaining the systemic vascular resistance, and also on the increase in cardiac output. An adrenergic innervation of the heart may play some role in the control of cardiac performance both at rest and during exercise, but the main cardioregulatory mechanism is likely to be non-adrenergic, most probably including cardiac control via variation of the cholinergic vagal cardioinhibitory tonus.

Central and regional hemodynamic effects during infusion of Big endothelin-1 in healthy humans

1996 ◽  
Vol 80 (6) ◽  
pp. 1921-1927 ◽  
Author(s):  
G. Ahlborg ◽  
A. Ottosson-Seeberger ◽  
A. Hemsen ◽  
J. M. Lundberg
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Systemic Vascular Resistance ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Mean Arterial Blood Pressure ◽  
Endothelin 1 ◽  
Healthy Humans ◽  
Arterial Blood

Big endothelin-1 (Big ET-1) was given intravenously to six healthy men to study uptakes and vascular effects. Blood samples were taken from systemic and pulmonary arterial and internal jugular and deep forearm venous catheters. Arterial Big ET-1-like immunoreactivity (Big ET-1-LI) increased from 5.43 +/- 0.60 to 756 +/- 27 pmol/l, and ET-1-LI increased from 4.67 +/- 0.08 to 6.67 +/- 0.52 pmol/l (P < 0.001). Skeletal muscle fractional extraction of Big ET-1-LI was 15 +/- 4%. ET-1-LI release did not increase in the studied vascular beds. Heart rate fell by 17% (P < 0.001), cardiac output fell by 26% (P < 0.001), and stroke volume fell by 11% (P < 0.05). Mean arterial blood pressure increased 18%, systemic vascular resistance increased 65%, and pulmonary vascular resistance increased 57% (P < 0.01-0.001). Pulmonary blood pressures, forearm blood flow, arterial pH, arterial PCO2, and systemic arterial-internal jugular venous O2 difference remained unchanged. No specific Big ET-1 receptors were found in human pulmonary membranes. The half-maximal inhibitory concentration for the receptor antagonist bosentan was 181 nM. In summary, circulating Big ET-1 elicits greater increases in mean arterial blood pressure and systemic vascular resistance and decreases in heart rate and cardiac output compared with an equimolar ET-1 infusion (26).

Gender differences in cardiovascular responses to the cold hand pressor test and facial cooling

1994 ◽  
Vol 72 (10) ◽  
pp. 1193-1199 ◽  
Author(s):  
R. D. Kilgour ◽  
J. Carvalho
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Cardiovascular Responses ◽  
Pressor Test ◽  
Arterial Blood ◽  
Facial Cooling

To test the hypothesis that changes in systemic vascular resistance (SVR) contribute to the differences in arterial blood pressure responses between men and women to local cold pressor tests, nine normotensive men (25.9 ± 5.9 years old) and women (24.4 ± 5.9 years old) performed the cold hand pressor test (CPT; 6 min in 5 °C water) in the supine position. A subgroup of men (n = 5) and women (n = 5) from the CPT were exposed to 6 min of facial cooling (FC) by circulating cold water (5 °C) through a perfusion mask. Using standard auscultatory techniques, pre-experimental systolic and diastolic blood pressures were found to be significantly higher (p ≤ 0.05) in males than females. During the initial 2 min of CPT and FC, both males and females experienced similar relative increases in pressure. Thereafter, only the males maintained an elevated pressor response, whereas the females progressively declined. The gender-related trends in blood pressure can be explained by differences in SVR, with the males exhibiting significantly greater changes in SVR than females during min 4–6 in CPT. Heart rate increased (p ≤ 0.05) in both groups, with the greater rise occurring in females at each minute of CPT. Throughout FC, the changes in SVR were similar between groups, with the exception of the 6-min value being greater than baseline in men but not women. No differences in heart rate or cardiac output were observed between groups during FC. In general, the results indicate that men respond with greater and more prolonged peripheral adjustments (e.g., rise in SVR), whereas females are more like "cardiac" responders, with greater increases in heart rate and an attenuated blood pressure response to CPT.Key words: cold pressor test, facial cooling, gender, systemic vascular resistance, heart rate.

Hemodynamic response to converting enzyme inhibition at rest and exercise in humans

1982 ◽  
Vol 53 (3) ◽  
pp. 576-581 ◽  
Author(s):  
R. Fagard ◽  
P. Lijnen ◽  
L. Vanhees ◽  
A. Amery
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Oxygen Uptake ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Plasma Renin ◽  
Peak Oxygen Uptake ◽  
Converting Enzyme

The response of the systemic circulation to acute inhibition of the converting enzyme with 25 mg of oral Captopril (Squibb) was studied in six normal sodium-replete male volunteers at rest and during exercise, together with its effects on exercise capacity for graded uninterrupted exercise. In recumbent subjects at rest Captopril did not affect arterial pressure or heart rate, and plasma renin activity rose 2.5-fold (P less than 0.05). In subjects in the sitting position, at rest and during exercise until exhaustion, Captopril reduced mean brachial intra-arterial pressure by an average of 7 Torr in comparison to placebo (P less than 0.001). Captopril's hypotensive effect was caused by a reduction of systemic vascular resistance (P less than 0.01), without changes of cardiac output (measured by CO2 rebreathing), heart rate, or stroke volume. Plasma renin activity was significantly higher during Captopril (P less than 0.001). Peak oxygen uptake and exercise duration were the same after administration of Captopril or placebo. The data demonstrate that the renin-angiotensin system is not involved in the homeostasis of blood pressure in supine sodium-replete humans, but has a modest role in blood pressure regulation when posture is changed from supine to upright. The orthostatic effect of Captopril is maintained during upright exercise. Furthermore the reduction of systemic vascular resistance by Captopril does not affect peak oxygen uptake.

Blood Volume and the Carotid Baroreceptor Reflex in Conscious Rabbits

1981 ◽  
Vol 61 (s7) ◽  
pp. 173s-175s ◽  
Author(s):  
J. Ludbrook ◽  
I. B. Faris ◽  
G. G. Jamieson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Systemic Vascular Resistance ◽  
Blood Volume ◽  
Vascular Resistance ◽  
Baroreceptor Reflex ◽  
Phase Lag ◽  
Carotid Baroreceptor ◽  
Conscious Rabbits

1. The effects of acute blood volume change in conscious rabbits on a.c. gain of the carotid baroreceptor reflex with respect to heart rate, blood pressure, cardiac output and systemic vascular resistance were studied. 2. With acute, isohaemic increase in blood volume by 20% and 40% the only consistent trend was a decrease in gain for systemic vascular resistance. 3. With acute reduction in blood volume there was a consistent tendency for gain for heart rate to fall. With 20% reduction in blood volume, gain for cardiac output fell but gain for systemic vascular resistance rose and its phase-lag became shorter, so that gain for blood pressure was unaltered. The enhanced gain for systemic vascular resistance was not sustained with 35% reduction in blood volume, so that gain for blood pressure fell. 4. Thus control of blood pressure by the carotid sinus reflex is remarkably unaffected by acute change in blood volume, and is impaired only when there is depression of gain for cardiac output without a concomitant rise in gain for systemic vascular resistance.

Clevidipine in Adult Cardiac Surgical Patients

2002 ◽  
Vol 96 (5) ◽  
pp. 1086-1094 ◽  
Author(s):  
James M. Bailey ◽  
Wei Lu ◽  
Jerrold H. Levy ◽  
James G. Ramsay ◽  
Linda Shore-Lesserson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Cardiac Index ◽  
Arterial Pressure ◽  
Calcium Channel ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Calcium Channel Antagonist ◽  
Surgical Patients

Background Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. Methods Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration-response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. Results There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. Conclusion Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.

Sympathetic vascular transduction is augmented in young normotensive blacks

2002 ◽  
Vol 92 (2) ◽  
pp. 651-656 ◽  
Author(s):  
Chester A. Ray ◽  
Kevin D. Monahan
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Forearm Blood Flow ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Arterial Blood ◽  
Blacks And Whites

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 ± 7 vs. 55 ± 18%, 81 ± 21 vs. 137 ± 42%, 174 ± 81 vs. 556 ± 98% for −5, −15, and −40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 ± 0.07 vs. 0.82 ± 0.07 U; 0.82 ± 0.11 vs. 0.64 ± 0.09 U; 0.95 ± 0.37 vs. 0.35 ± 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

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