Role of respiratory motor output in within-breath modulation of muscle sympathetic nerve activity in humans.
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We measured muscle sympathetic nerve activity (MSNA, peroneal microneurography) in 5 healthy humans under conditions of matched tidal volume, breathing frequency, and end-tidal CO(2), but varying respiratory motor output as follows: (1) passive positive pressure mechanical ventilation, (2) voluntary hyperventilation, (3) assisted mechanical ventilation that required the subject to generate -2.5 cm H(2)O to trigger each positive pressure breath, and (4) added inspiratory resistance. Spectral analyses showed marked respiratory periodicities in MSNA; however, the amplitude of the peak power was not changed with changing inspiratory effort. Time domain analyses showed that maximum MSNA always occurred at end expiration (25% to 30% of total activity) and minimum activity at end inspiration (2% to 3% of total activity), and the amplitude of the variation was not different among conditions despite marked changes in respiratory motor output. Furthermore, qualitative changes in intrathoracic pressure were without influence on the respiratory modulation of MSNA. In all conditions, within-breath changes in MSNA were inversely related to small changes in diastolic pressure (1 to 3 mm Hg), suggesting that respiratory rhythmicity in MSNA was secondary to loading/unloading of carotid sinus baroreceptors. Furthermore, at any given diastolic pressure, within-breath MSNA varied inversely with lung volume, demonstrating an additional influence of lung inflation feedback on sympathetic discharge. Our data provide evidence against a significant effect of respiratory motor output on the within-breath modulation of MSNA and suggest that feedback from baroreceptors and pulmonary stretch receptors are the dominant determinants of the respiratory modulation of MSNA in the intact human. (+info)
Summation of dynamic transfer characteristics of left and right carotid sinus baroreflexes in rabbits.
(18/1182)
Although interactions among parallel negative-feedback baroreflex systems have been extensively investigated with respect to their steady-state responses, the dynamic interactions remain unknown. In anesthetized, vagotomized, and aortic-denervated rabbits, we perturbed isolated intracarotid sinus pressure (CSP) unilaterally or bilaterally around the physiological operating pressure according to binary white noise. The neural arc transfer function from CSP to cardiac sympathetic nerve activity (SNA) and the peripheral arc transfer function from SNA to aortic pressure were estimated. The gain values of the neural arc at 0.01 Hz estimated by the left (L) and right (R) CSP perturbations were 0.94 +/- 0.31 and 0.96 +/- 0.25, respectively. The gain value increased to 2.17 +/- 0.97 during the bilateral identical CSP perturbation and was not significantly different from L + R. The phase values of the neural arc did not differ among protocols. No significant differences were observed in the peripheral arc transfer functions among protocols. We conclude that summation of the dynamic transfer characteristics of the bilateral carotid sinus baroreflexes around the physiological operating pressure approximates simple addition. (+info)
Relationship between baroreceptor reflex function and end-organ damage in spontaneously hypertensive rats.
(19/1182)
The purpose of this study was to further illustrate the relationship between baroreceptor reflex sensitivity (BRS) and hypertensive end-organ damage (EOD) and to test the hypothesis that impairment of BRS aggravates EOD in hypertension. We studied baroreflex-mediated changes in heart rate [expressed as baroreceptor sensitivity to heart rate control (BRS(HR))] and blood pressure [expressed as baroreceptor sensitivity to blood pressure control (BRS(BP))] in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) that were used as controls, both at the age of 50-52 wk. Rats were also instrumented to record BP, HR, and BP variability (BPV) in the conscious, unrestrained state. In SHR compared with WKY, BP and BPV were significantly increased, whereas BRS(HR) and BRS(BP) were significantly decreased. SHR had remarkable EOD when compared with WKY (EOD score: 6.3 +/- 2.5 vs. 2.9 +/- 0.8, P < 0.01). Univariate regressive analysis demonstrated that EOD score was increased with BP and BPV and decreased with BRS. In multivariate analysis, EOD score was predicted by greater systolic BP and lower BRS and HR variability. These results indicate that BRS is negatively related to BPV and EOD score, and impaired BRS might be one of the major causes for hypertensive EOD. (+info)
Graded and dynamic reflex summation of myelinated and unmyelinated rat aortic baroreceptors.
(20/1182)
Unmyelinated (C) and myelinated (A) baroreceptor (BR) axons are present in rat aortic depressor nerve (ADN). With graded ADN electrical activation and anodal conduction blockade, reflex responses in anesthetized rats were assessed as changes in mean arterial pressure (MAP) and heart rate (HR). We tested the hypothesis that C-type BR inputs are effective at low frequencies because they outnumber A-type. Anodal current (Ian) reversibly eliminated all MAP and HR responses to A-selective stimuli. High intensities activated all ADN axons (A+C) and decreased MAP at lower frequencies (<10 Hz) than were effective with A-selective stimulation. I(an) reduced only MAP responses to >10-Hz ADN stimulation. Burst patterns significantly augmented A- but not C-selective reflex responses despite identical numbers of shocks per second. A-selective stimuli failed to evoke significant bradycardia even at 200 Hz. Maximum intensity stimuli plus Ian (C selective) evoked less bradycardia than without I(an) (A+C), indicating supra-additive summation unlike the occlusive summation for MAP responses. However, activation of reduced numbers of C-type BRs with all A-type BRs suggests a strong A to C interaction in reflex bradycardia responses. Surprisingly, Ian block of A-type conduction eliminated all reflex bradycardia at such submaximal intensities despite C conduction and depressor responses. A- and C-type BRs act synergistically, and A-type activity is absolutely required in cardiac but not in depressor pathways. Thus greater numbers do not appear to account for C-type BR efficacy, and critical interactions between these two sensory subtypes appear to occur differentially across cardiac and systemic baroreflex effector pathways. (+info)
Cardiovascular afferent signals and drinking in response to hypotension in dogs.
(21/1182)
Arterial hypotension stimulates increases in plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake in conscious dogs. We have previously reported that increasing left atrial but not right atrial pressure completely blocks the increase in plasma AVP and PRA induced by hypotension. The goal of the present study was to examine the effect of increasing right or left atrial pressure on water intake induced by arterial hypotension. Dogs were prepared with occluding cuffs on the thoracic inferior vena cava, the pulmonary artery, and the ascending aorta. We reduced mean arterial pressure (MAP) 25% below control by either inferior vena cava constriction (IVCC), pulmonary artery constriction (PAC), or ascending aorta constriction (AAC) and measured water intake over a 2-h period. Cumulative water intake during IVCC (n = 6) and PAC (n = 6) was 7.8 +/- 2.0 and 6.7 +/- 2.6 ml/kg, respectively. There was no difference between either the latency or the volume consumed between the two treatments. In contrast, none of the dogs drank during hypotension induced by AAC (n = 5). Because the degree of arterial baroreceptor unloading was the same in each treatment by design, we conclude that stimulation of left atrial receptors inhibits drinking in response to arterial hypotension but that stimulation of right atrial receptors has no effect on the response in dogs. (+info)
Arterial pressure in humans during weightlessness induced by parabolic flights.
(22/1182)
Results from our laboratory have indicated that, compared with those of the 1-G supine (Sup) position, left atrial diameter (LAD) and transmural central venous pressure increase in humans during weightlessness (0 G) induced by parabolic flights (R. Videbaek and P. Norsk. J. Appl. Physiol. 83: 1862-1866, 1997). Therefore, because cardiopulmonary low-pressure receptors are stimulated during 0 G, the hypothesis was tested that mean arterial pressure (MAP) in humans decreases during 0 G to values below those of the 1-G Sup condition. When the subjects were Sup, 0 G induced a decrease in MAP from 93 +/- 4 to 88 +/- 4 mmHg (P < 0.001), and LAD increased from 30 +/- 1 to 33 +/- 1 mm (P < 0.001). In the seated position, MAP also decreased from 93 +/- 6 to 87 +/- 5 mmHg (P < 0.01) and LAD increased from 28 +/- 1 to 32 +/- 1 mm (P < 0.001). During 1-G conditions with subjects in the horizontal left lateral position, LAD increased compared with that of Sup (P < 0.001) with no further effects of 0 G. In conclusion, MAP decreases during short-term weightlessness to below that of 1-G Sup simultaneously with an increase in LAD. Therefore, distension of the heart and associated central vessels during 0 G might induce the hypotensive effects through peripheral vasodilatation. Furthermore, the left lateral position in humans could constitute a simulation model of weightlessness. (+info)
Diverse effects of AT1 receptor antagonists on normal blood pressure and regulatory system.
(23/1182)
An AT1 receptor antagonist, losartan, has been reported to improve survival and quality of life in patients with congestive heart failure as angiotensin converting enzyme inhibitors do. Since many of the patients are normotensive, it may be a drawback if the compound decreases normal blood pressure. In this study, we investigated whether a novel AT1 receptor antagonist, TA-606, which is more potent than losartan, affects normal blood pressure and its regulatory system in comparison with losartan. TA-606 (30 and 100 mg/kg, p.o.) did not change normal blood pressure, whereas losartan (100 mg/kg, p.o.) tended to decrease it. Although EXP3174 (1 and 10 mg/kg, i.v.), an active metabolite of losartan, suppressed the baroreceptor-heart rate (HR) reflex, 606A (1 and 10 mg/kg, i.v.), an active metabolite of TA-606, did not affect it. Since losartan is known to affect the L-glutamate receptor which is part of the central blood pressure regulatory system, we also investigated whether 606A affects L-glutamate receptor binding. We found that 606A did not affect the binding of the L-glutamate receptor, but EXP3174 inhibited the binding with IC50 values of 13.3 microM. These findings suggest that, even having the same AT1 receptor antagonist properties as losartan and EXP3174, TA-606 and its active metabolite do not influence normal blood pressure or its regulatory system. (+info)
Pathophysiological roles of endothelin-1 in Dahl salt-sensitive hypertension.
(24/1182)
The purpose of the present experiment was to study the pathophysiological roles of endothelin-1 (ET-1) in salt-sensitive hypertension with the use of Dahl salt-sensitive (DS) and salt-resistant (DR) rats. PreproET-1 mRNA expression was determined by reverse transcription-polymerase chain reaction. In the kidney, expression of preproET-1 mRNA was greater in DS rats on a normal salt diet compared with DR rats of the same age. In DS rats, the level of preproET-1 mRNA expression in kidney had a significant correlation with systolic blood pressure. The expression of preproET-1 mRNA in aorta and kidney was increased by 3-week high salt intake in DS rats but not in DR rats. Expression of preproET-1 mRNA and ET-1 levels in left ventricle was exaggerated by high salt intake in DS rats. However, there was no significant difference in plasma ET-1 levels between DS and DR rats regardless of salt intake. Pressor response curves for ET-1 in DS rats with or without high salt intake were significantly shifted to the left compared with those in DR rats. A single oral dose (3 to 10 mg/kg) of J-104132 (L-753 037), a potent, orally active mixed endothelin A and B (ET(A)/ET(B)) receptor antagonist, reduced blood pressure to normotensive levels in DS rats with high salt intake, and its action was maintained for >/=24 hours. In DS rats with normal salt intake, J-104132 (10 mg/kg) slightly but significantly decreased blood pressure. DR rats did not show obvious depressor responses to J-104132 (10 mg/kg) regardless of salt intake. These results suggest that ET-1 acts as one of the pathophysiological factors in the development and maintenance of salt-sensitive hypertension, and a mixed ET(A)/ET(B) receptor antagonist could be useful in the treatment for salt-sensitive hypertension. (+info)