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As our understanding of the importance of individualized medicine continues to grow, the clinical relevance of interindividual variability in hemodynamic variables is receiving increasing attention. However, it is not known whether the rat, which is often used for studies of cardiovascular regulation, exhibits similar interindividual variability. In the present study, we evaluated whether the magnitude of interindividual variability in cardiac output (CO) and total peripheral resistance (TPR) was similar in humans and in rats. We assessed interindividual variability of mean arterial pressure (MAP), CO, and TPR during control conditions in normotensive humans (n = 40) and during normotension and deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats (n = 16). Humans and rats showed marked interindividual variability in CO and TPR but low variability in MAP. During deoxycorticosterone acetate-salt hypertension, CO was maintained, but TPR was elevated compared with the baseline period. We conclude that the magnitudes of interindividual variability of MAP, CO, and TPR are quantitatively similar in humans and rats, providing support for the relevance of this variability in both species and suggesting that studies in rats could be designed to address questions specific to individualized medicine in hypertension. circulation; cardiac output; vasoconstriction; arterial pressure; sympathetic nervous system doi:10.1152/ajpregu.00607.2009

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor [N.sup.G]-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA ([P.sub.ANOVA] < 0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n = 6, 28 [+ or -] 4 bursts/100 heartbeats), AP increased 9 [+ or -] 1 mmHg, whereas in the high-MSNA subgroup (n = 6, 58 [+ or -] 3 bursts/100 heartbeats), AP increased 15 [+ or -] 2 mmHg (P < 0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation. hypertension; cardiac output; sympathetic nervous system doi:10.1152/ajpheart.00234.2006

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 [+ or -] 1 mosmol/kg in C to 290 [+ or -] 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 [+ or -] 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HTI, but both increased slightly in HT2. HR increased slightly but significantly during both HTI and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 [+ or -] 0.97 (HT1) vs. -5.85 [+ or -] 0.63 (C) arbitrary units (au)*[beat.sup.-1]*mm[Hg.sup.-1]; P < 0.01] but was not different in HT2 (-6.55 [+ or -] 0.94 au*[beat.sup.-1]*mm[Hg.sup.-1]). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP. baroreflex; sympathetic nervous system; hydration; plasma volume

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia during orthostasis. To test the hypothesis that patients with POTS have decreased sympathetic neural responses to baroreflex stimuli, we measured heart rate (HR) and muscle sympathetic nerve activity (MSNA) responses to three baroreflex stimuli including vasoactive drug boluses (modified Oxford technique), Valsalva maneuver, and head-up tilt (HUT) in POTS patients and healthy control subjects. The MSNA response to the Valsalva maneuver was significantly greater in the POTS group (controls, 26 [+ or -] 7 vs. POTS, 48 [+ or -] 6% of baseline MSNA/mmHg; P = 0.03). POTS patients also had an exaggerated MSNA response to 30[degrees] HUT (controls, 123 [+ or -] 24 vs. POTS, 208 [+ or -] 30% of baseline MSNA; P = 0.03) and tended to have an exaggerated response to 45[degrees] HUT (controls, 137 [+ or -] 27 vs. POTS, 248 [+ or -] 58% of baseline MSNA; P = 0.10). Sympathetic baroreflex sensitivity calculated during administration of the vasoactive drug boluses also tended to be greater in the POTS patients; however, this did not reach statistical significance (P = 0.15). Baseline MSNA values during supine rest were not different between the groups (controls, 23 [+ or -] 4 vs. POTS, 16 [+ or -] 5 bursts/100 heartbeats; P = 0.30); however, resting HR was significantly higher in the POTS group (controls, 58 [+ or -] 3 vs. POTS, 82 [+ or -] 4 beats/rain; P = 0.0001). Our results suggest that POTS patients have exaggerated MSNA responses to baroreflex challenges compared with healthy control subjects, although resting supine MSNA values did not differ between the groups. intolerance; blood pressure; heart rate; Valsalva maneuver; head-up tilt

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans. Am J Physiol Heart Circ Physio1 287: H1658-H1662, 2004. First published June 10, 2004: 10A152/ajpheart00265.2004--Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10[degrees] head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased ~2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 [+ or -] 0.6 and -3.3 [+ or -] 1.0 versus -5.0 [+ or -] 0.6 units*[beat.sup.-1]*mm[Hg.sup.-1] (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans. sympathetic nervous system; blood pressure regulation; volume; circulation

To determine whether, in the presence of constant insulin concentrations, a change in glucose concentrations results in a reciprocal change in endogenous glucose production (EGP), glucagon (~130 ng/l) and insulin (~65 pmol/l) were maintained at constant 'basal' concentrations while glucose was clamped at ~5.3 mM (euglycemia), ~7.0 mM (sustained hyperglycemia; n = 10), or varied to create a 'postprandial' profile (profile; n = 11). EGP fell slowly over the 6 h of the euglycemia study. In contrast, an increase in glucose to 7.13 [+ or -] 0.3 mmol/l resulted in prompt and sustained suppression of EGP to 9.65 [+ or -] 1.21 [micro]mol * [kg.sup.-1] * [min.sup.-1]. On the profile study day, glucose increased to a peak of 11.2 [+ or -] 0.5 mmol/l, and EGP decreased to a nadir of 6.79 [+ or -] 2.54 [micro]mol * [kg.sup.-1] * [min.sup.-1] by 60 min. Thereafter, the fall in glucose was accompanied by a reciprocal rise in EGP to rates that did not differ from those observed on the euglycemic study day (11.31 [+ or -] 2.45 vs. 12.11 [+ or -] 3.21 [micro]mol * [kg.sup.-1] * [min.sup.-1]). Although the pattern of change of glucose differed markedly on the sustained hyperglycemia and profile study days, by design the area above basal did not. This resulted in equivalent suppression of EGP below basal (-1,952 [+ or -] 204 vs. -1,922 [+ or -] 246 mmol * [kg.sup.-1] * 6[h.sup.-1]). These data demonstrate that, in the presence of a constant basal insulin concentration, changes in glucose within the physiological range rapidly and reciprocally regulate EGP. glucose effectiveness; glucose turnover

Acute β-adrenergic blockade increases aortic wave reflection; however, the mechanisms remain unclear. Evidence suggests that β-adrenergic receptor sensitivity in the peripheral vasculature differs between sexes. Therefore, the goal of this study was to examine whether β-adrenergic blockade alters aortic wave reflection to a similar extent in young men and women. In 31 subjects (16 men and 15 women; 26±1 years) noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and during systemic β-blockade (0.25 mg/kg bolus, followed by 0.004 mg/kg per minute of continuous infusion of propranolol). β-Blockade increased aortic augmentation index and wave reflection amplitude (aortic augmented pressure) in both sexes (P<0.01). Although the increase in augmentation index was not significantly different between sexes (7.5±1.1% versus 4.6±1.5%; P=0.07), the increase in aortic augmented pressure was greater in women compared with men (2.8±0.5 versus 1.4±0.5 mm Hg; P<0.05). Aortic augmentation index adjusted for a heart rate of 75 bp increased in women (4.1±1.1%; P<0.05) after β-blockade, whereas it was unchanged in men (0.6±1.3%; P=0.33). Moreover, the change in aortic augmentation index was inversely associated with the change in heart rate only in men (r=-0.54; P<0.05). Our data suggest that aortic wave reflection is increased to a greater extent in women after systemic β-blockade, and enhanced aortic wave reflection appears to be mediated by a reduced heart rate in men, whereas the mechanism is unclear in women. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system plays a key role in regulating arterial blood pressure in humans. This review provides an overview of sympathetic neural control of the circulation and discusses the changes that occur in various disease states, including hypertension, heart failure, and obstructive sleep apnea. It focuses on measurements of sympathetic neural activity (SNA) obtained by microneurography, a technique that allows direct assessment of the electrical activity of sympathetic nerves in conscious human beings. Sympathetic neural activity is tightly linked to blood pressure via the baroreflex for each individual person. However, SNA can vary greatly among individuals and that variability is not related to resting blood pressure; that is, the blood pressure of a person with high SNA can be similar to that of a person with much lower SNA. In healthy normotensive persons, this finding appears to be related to a set of factors that balance the variability in SNA, including cardiac output and vascular adrenergic responsiveness. Measurements of SNA are very reproducible in a given person over a period of several months to a few years, but SNA increases progressively with healthy aging. Cardiovascular disease can be associated with substantial increases in SNA, as seen for example in patients with hypertension, obstructive sleep apnea, or heart failure. Obesity is also associated with an increase in SNA, but the increase in SNA among patients with obstructive sleep apnea appears to be independent of obesity per se. For several disease states, successful treatment is associated with both a decrease in sympathoexcitation and an improvement in prognosis. This finding points to an important link between altered sympathetic neural mechanisms and the fundamental processes of cardiovascular disease. [ABSTRACT FROM AUTHOR]