Relating drug-induced changes in carotid artery mechanics to cardiovagal and sympathetic baroreflex control

Previous evidence indicates that sensitivity of the baroreflex cardiovagal and sympathetic arms is dissociated. In addition, pharmacologic assessment of baroreflex sensitivity (BRS) has revealed that cardiovagal, but not sympathetic, BRS is greater when blood pressure is increasing versus falling. The origin of this hysteresis is unknown. In this study, carotid artery distensibility and absolute distension (diameter) were assessed to test the hypothesis that vessel mechanics in barosensitive regions affect the BRS of cardiovagal, but not sympathetic, outflow. R-R interval (i.e. time between successive R waves), finger arterial blood pressure, muscle sympathetic nerve activity, and carotid artery dimensions (B-mode imaging) were measured during sequential infusions of sodium nitroprusside (SNP) and phenylephrine (PHE). Systolic and diastolic common carotid artery diameters and pulse pressure were recorded to calculate distensibility of this vessel under each drug condition. Cardiovagal BRS was greater when blood pressure was increasing versus decreasing (p < 0.01). Sympathetic BRS was not affected by direction of pressure change. Distensibility did not differ between SNP and PHE injections. However, compared with SNP, infusion of PHE resulted in larger absolute systolic and diastolic carotid diameters (p < 0.001). Therefore, cardiovagal reflex hysteresis was related to drug-induced changes in common carotid artery diameter but not distensibility. The lack of sympathetic hysteresis in this model suggests a relative insensitivity of this baroreflex component to carotid artery dimensions and provides a possible mechanism for the dissociation between cardiovagal and sympathetic BRS.     

Effect of lymphatic outflow pressure on lymphatic albumin transport in humans.

The effects of posture on the lymphatic outflow pressure and lymphatic return of albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate conditions: upright rest (Up), upright rest with lower body positive pressure (LBPP), supine rest (Sup), and supine rest with lower body negative pressure (LBNP). The increase in plasma albumin content (Delta Alb) during the 2 h after bolus saline infusion was greater in Up than in LBPP: 82.9 +/- 18.5 vs. -28.4 mg/kg body wt. Delta Alb was greater in LBNP than in Sup: 92.6 vs. -22.5 +/- 18.9 mg/kg body wt (P < 0.05). The greater Delta Alb in Up and Sup with LBNP were associated with a lower estimated lymphatic outflow pressure on the basis of the difference in central venous pressure (Delta CVP). During LBPP, CVP was increased compared with Up: 3.8 +/- 1.4 vs. -1.2 +/- 1.2 mmHg. During LBNP, CVP was reduced compared with Sup: -3.0 +/- 2.2 vs. 1.7 +/- 1.0 mmHg. The translocation of protein into the vascular space after bolus saline infusion reflects lymph return of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow pressure. Thus posture-dependent changes in lymphatic protein transport are modulated by changes in CVP through its mechanical impact on lymphatic outflow pressure.     

Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery

We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery would be impaired by acute increases in sympathetic nervous system activity (SNA) in models where similar peak shear stress stimulus was achieved by varying the duration of forearm muscle ischemia. Eleven healthy young men were studied under four different conditions, each with its own control: lower body suction (LBS), cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle chemoreflex (MCR). The duration of ischemia before observation of FMD by ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2-min for MCR. Peak shear rate was not different between control and any of the SNA conditions, although total shear in the first minute was reduced in MAT. MCR was the only condition in which brachial artery vasoconstriction was observed before forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P < 0.05]; however, diameter increased to the same absolute value as that of the control, so the percent FMD was greater for MCR [9.85 (SD 2.33) vs. control 5.29 (SD 1.50)%]. Blunting of the FMD response occurred only in the CPT model [1.51 (SD 1.20)%]. During SNA, the increase in plasma cortisol from baseline was significant only for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and CPT; and the increase in epinephrine was significant only for MCR. These results showed that the four models employed to achieve increases in SNA had different effects on baseline brachial artery diameter and that blunted FMD is not a general response to increased SNA.     

Relationship between changes in brachial artery flow-mediated dilation and basal release of nitric oxide in subjects with Type 2 diabetes

Assessment of flow-mediated dilation (FMD) after forearm ischemia is widely used as a noninvasive bioassay of stimulated nitric oxide (NO)-mediated conduit artery vasodilator function in vivo. Whether this stimulated endothelial NO function reflects basal endothelial NO function is unknown. To test this hypothesis, retrospective analysis of randomized crossover studies was undertaken in 17 subjects with Type 2 diabetes; 9 subjects undertook an exercise training or control period, whereas the remaining 8 subjects were administered an angiotensin II receptor blocker or placebo. FMD was assessed by using wall tracking of high-resolution brachial artery ultrasound images in response to reactive hyperemia. Resistance vessel basal endothelium-dependent NO function was assessed by using intrabrachial administration of NG-monomethyl-L-arginine (L-NMMA) and plethysmographic assessment of forearm blood flow (FBF). FMD was higher after intervention compared with control/placebo (6.15+/-0.53 vs. 3.81+/-0.72%, P<0.001). There were no significant changes in the FBF responses to L-NMMA. Regression analysis between FMD and L-NMMA responses at entry to the study revealed an insignificant correlation (r=-0.10, P=0.7), and improvements in FMD with the interventions were not associated with changes in the L-NMMA responses (r=-0.04, P=0.9). We conclude that conduit artery-stimulated endothelial NO function (FMD) does not reflect basal resistance vessel endothelial NO function in subjects with Type 2 diabetes.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Sustained increases in sympathetic outflow during prolonged lower body negative pressure in humans

The purpose of this study was to determine whether prolonged unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP) causes constant increases in sympathetic outflow to skeletal muscles. Eight healthy subjects underwent a 20-min control period followed by 20 min of 15-mmHg LBNP. This pressure was selected because it did not cause any significant change in mean arterial blood pressure (sphygmomanometry) or heart rate, suggesting that the cardiopulmonary baroreceptors were selectively unloaded and the activity of the arterial baroreceptors was unchanged. Muscle sympathetic nerve activity in the peroneal nerve (MSNA, microneurography) increased from an average of 21.8 +/- 1.7 bursts/min over the last 5 min of control to 29.0 +/- 2.9 bursts/min during the 1st min of LBNP (P less than 0.05 LBNP vs. control). The increase in MSNA observed during the 1st min was sustained throughout LBNP. Forelimb blood flow (plethysmography) decreased abruptly at the onset of the LBNP from a control value of 4.3 +/- 0.5 ml.min-1.100 ml-1 to 2.5 +/- 0.2 at the 1st min; the flow then increased and remained significantly above this value, but below the control value, throughout LBNP. Similar blood flow findings were obtained in additional studies, when the hand circulation was excluded during the flow measurements. Forearm skin blood flow (laser Doppler) also decreased abruptly at the onset of LBNP and was followed by partial recovery, but these changes were too small to account for all the increases in limb blood flow over the course of LBNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic nerve activity in arm and leg muscles during lower body negative pressure in humans

Nonhypotensive lower body negative pressure (LBNP) is reported to decrease forearm but not calf blood flow as measured by strain-gauge plethysmography. This suggests that unloading of cardiopulmonary receptors increases sympathetic outflow to arm but not to leg. To test this hypothesis we measured muscle sympathetic nerve activity (MSA) in the arm (radial nerve) and leg (peroneal nerve) simultaneously during LBNP. In eight healthy subjects, we measured heart rate, blood pressure, and radial and peroneal MSA during LBNP at 10 and 20 mmHg. There was no difference between radial and peroneal MSA at rest, and there were successive parallel increases of MSA in both nerves during LBNP at 10 and 20 mmHg. These data indicate that there are nearly identical increases of sympathetic outflow to the arm and leg during mild to moderate degrees of orthostatic stress.     

Evidence for reduced sympatholysis in leg resistance vasculature of healthy older women

Inhibition of a sympathetic stimulus (i.e., sympatholysis) during forearm exercise is reduced with age in women. This age-related alteration has not been characterized in the lower extremity vasculature of women, and the potential for blunting of the conduit artery dilatory response to a sudden increase in shear stress [flow-mediated dilation (FMD)] has not been examined in older adults of either sex. In the present study, we assessed popliteal artery diameter and velocity (Doppler ultrasound) in 16 young (23 +/- 1 yr) and 14 older (69 +/- 1 yr) women after 5 min of distal calf occlusion (FMD), 3 min of hand immersion in ice water [cold pressor test (CPT)], and 5 min of distal calf occlusion combined with hand immersion in ice water (FMD+CPT). Peak popliteal conductance after 5-min ischemia was not significantly different in young vs. older women. During the combined stimulus (FMD+CPT), the magnitude of vasoconstriction in the calf (reduction in peak popliteal artery conductance) was similar (5-8%), despite reduced resting adrenergic sensitivity to CPT [young (Y): -27.3 +/- 3.8%; older (O): -15.8 +/- 2.2%; P < 0.05] and blunted muscle sympathetic nerve activity responses to CPT (Y: 12.7 +/- 3.6 bursts/min; O: 7.8 +/- 2.5 bursts/min; P < 0.05) in older women. Popliteal FMD, normalized to the shear stimulus, was attenuated by 60-70% in older women. Peak popliteal diameter, measured during the combined stimulus (FMD+CPT), was blunted in young but not in older women (Y FMD: 5.5 +/- 0.1 mm; Y FMD+CPT: 5.4 +/- 0.1 mm; P = 0.03; O FMD: 5.8 +/- 0.2 mm; O FMD+CPT: 5.8 +/- 0.2 mm). These results confirm previous findings of diminished reactivity in the conduit arteries of older humans and provide the first evidence of reduced sympatholysis in the leg resistance vasculature of older women.     

WISE 2005: flow and nitroglycerin mediated dilation following 56 days of head down tilt bed rest with and without an exercise countermeasure

This investigation set out to determine the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on endothelial dependent and independent vascular function. 24women took part in this study. 8 subjects completed lower body resistance and aerobic exercise (EX, treadmill running 3-4 days per week for 40-min followed by 10-min of static LBNP, and resistive exercise on a flywheel device every 3rd day) and 16 subjects were considered as non-exercisers in a control group and a protein supplement group. FMD was induced by release of distal limb ischemia and NMD by sublingual administration of 0.3 mg of nitroglycerin before and after HDBR. Preliminary results of this study suggest that HDBR without EX results in a decreased resting diameter of the popliteal while EX increased the diameter. It is also suggested that FMD was elevated without exercise in both brachial and popliteal arteries, while pre-HDBR FMD was preserved by EX in the popliteal, but not the brachial artery. NMD appears to be elevated in the popliteal and femoral in the absence of exercise, but unchanged in the brachial artery or at any site for EX.     

Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise.

The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during -60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by approximately 45%. Mean arterial blood pressure was not significantly changed (P = 0.196), but diastolic blood pressure was elevated by approximately 10% and pulse pressure was reduced by approximately 20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP (P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in control vs. only 101.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.     

Effects of the cold pressor test on cardiac autonomic control in normal subjects

The cold pressor test (CPT) triggers in healthy subjects a vascular sympathetic activation and an increase in blood pressure. The heart rate (HR) response to this test is less well defined, with a high inter-individual variability. We used traditional spectral analysis together with the non-linear detrended fluctuation analysis to study the autonomic control of HR during a 3-min CPT. 39 healthy young subjects (23.7+/-3.2 years, height 180.4+/-4.7 cm and weight 73.3+/-6.4 kg) were divided into two groups according to their HR responses to CPT. Twenty subjects have a sustained increase in HR throughout the test with reciprocal autonomic interaction, i.e. increase in sympathetic activity and decrease vagal outflow. In the 19 remainders, HR decreased after an initial increase, with indication of involvement of both sympathetic and vagal outflow. Baseline evaluation of the subjects revealed no difference between the two groups. Nevertheless, a higher sympathetic activity at the skin level during CPT was present in the group with decreased HR. Further studies are needed to explain why healthy subjects react differently to the CPT and if this has potential clinical implications.     

Effect of cardiac pacing on forearm vascular responses and nitric oxide function

We examined the hypothesis that changes in heart rate at rest influence bioactivity of nitric oxide (NO) in humans by examining forearm blood flow responses during cardiac pacing in six subjects. Peak forearm and mean forearm blood flows across the cardiac cycle were continuously recorded at baseline and during pacing, with the use of high-resolution brachial artery ultrasound and Doppler flow velocity measurement. The brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA). As heart rate increased, no changes in pulse pressure and mean or peak blood flow were evident. L-NMMA had no effect on brachial artery diameter, velocity, or flows compared with saline infusion. These results contrast with our recent findings that exercise involving the lower body, associated with increases in heart rate and pulse pressure, also increased forearm blood flow, the latter response being diminished by L-NMMA. These data suggest that changes in blood pressure, rather than pulse frequency, may be the stimulus for shear stress-mediated NO release in vivo.     

Cardiopulmonary baroreflexes do not modulate exercise-induced sympathoexcitation

The purpose of this study was to test the general hypothesis that sympathoinhibitory cardiopulmonary baroreflexes modulate sympathetic outflow during voluntary exercise in humans. Direct (microneurographic) measurements of postganglionic sympathetic nerve activity to noncontracting muscle (MSNA) were made from the right peroneal nerve in the leg, and arterial pressure (AP) and heart rate (HR) were recorded in 10 healthy subjects before (control) and for 2.5 min during each of five interventions: 1) lower-body negative pressure at -10 mmHg (LBNP) alone, 2 and 3) isometric handgrip exercise at 15 and 30% of maximal voluntary contraction (MVC) alone, and 4 and 5) handgrip at 15 and 30% MVC performed during LBNP. During LBNP alone, which should have reduced cardiopulmonary baroreflex sympathoinhibition, AP and HR did not change from control, but MSNA increased 93 +/- 24% (P less than 0.05). Handgrip elicited contraction intensity-dependent increases in AP and HR (P less than 0.05), but MSNA increased above control only at the 30% MVC level (165 +/- 30%, P less than 0.05). The HR, AP, and MSNA responses to either level of handgrip performed during LBNP were not different from the algebraic sums of the corresponding responses to handgrip and LBNP performed separately (P greater than 0.05). Since there was no facilitation of the MSNA response to handgrip when performed during LBNP compared with algebraic sums of the separate responses, our results do not support the hypothesis that cardiopulmonary baroreflexes modulate (inhibit) sympathetic outflow during exercise in humans.     

Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans

Muscle sympathetic nerve activity (MSNA) is altered by vestibular otolith stimulation. This study examined interactive effects of the vestibular system and baroreflexes on MSNA in humans. In study 1, MSNA was measured during 4 min of lower body negative pressure (LBNP) at either -10 or -30 mmHg with subjects in prone posture. During the 3rd min of LBNP, subjects lowered their head over the end of a table (head-down rotation, HDR) to engage the otolith organs. The head was returned to baseline upright position during the 4th min. LBNP increased MSNA above baseline during both trials with greater increases during the -30-mmHg trial. HDR increased MSNA further during the 3rd min of LBNP at -10 and -30 mmHg (Delta32% and Delta34%, respectively; P < 0.01). MSNA returned to pre-HDR levels during the 4th min of LBNP when the head was returned upright. In study 2, MSNA was measured during HDR, LBNP, and simultaneously performed HDR and LBNP. The sum of MSNA responses during individual HDR and LBNP trials was not significantly different from that observed during HDR and LBNP performed together (Delta131 +/- 28 vs. Delta118 +/- 47 units and Delta340 +/- 77 vs. Delta380 +/- 90 units for the -10 and -30 trials, respectively). These results demonstrate that vestibular otolith stimulation can increase MSNA during unloading of the cardiopulmonary and arterial baroreflexes. Also, the interaction between the vestibulosympathetic reflex and baroreflexes is additive in humans. These studies indicate that the vestibulosympathetic reflex may help defend against orthostatic challenges in humans by increasing sympathetic outflow.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at -35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at -15 mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at -35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.     

Sympathetic vascular transduction is augmented in young normotensive blacks.

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.     

Relationship between blood pressure,sleep K-complexes,and muscle sympathetic nerve activity in humans

Stage 2 sleep is characterized by the EEG appearance of "K-complexes" and blood pressure oscillations. K-complexes may be directly related to blood pressure changes or they may reflect central sympathetic activation. We analyzed the temporal relationship among K-complexes, heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) during sleep in eight healthy volunteers (3 men and 5 women, age 22-41 yr). Most K-complexes presented as single large complexes (56 +/- 20%), followed by single small complexes (15 +/- 14%) and as couplets or triplets (13 +/- 6%). Single large K-complexes were preceded by a baroreflex-mediated increase of MSNA in approximately one-half (55%) of the cases. Detailed analysis of HR, BP, and MSNA was possible in 63 (45%) large single K-complexes not disturbed by preceding baroreflex-related changes. Systolic and diastolic BP and MSNA increased significantly after single events (22.5 +/- 13, 5.2 +/- 2.1, and 6.5 +/- 3.0%). Mean sympathetic baroreflex latency was similar after the single large K-complexes compared with the mean value during stage 2 sleep (1,290 +/- 126 vs. 1,279 +/- 61 ms). The area under the burst was significantly increased after single large K-complexes (median 3.9 vs. 9.0 arbitrary units, P < 0.03). The results support the hypothesis that K-complexes express cortical activation leading to temporary facilitation of sympathetic outflow in a graded fashion. Their functional effects appear to be independent of baroreflex modulation of MSNA in approximately 50% of the cases.     

肱动脉内皮依赖性舒张功能鉴别左室舒张功能假性正常化的价值

目的:研究冠心病患者左室舒张功能假性正常化与肱动脉内皮依赖性舒张功能的关系。方法:将75例行选择性冠状动脉造影的患者按冠状动脉病变程度分为单/双支病变组和三支病变组两组,选取48例健康志愿者作为对照组。检测左室舒张功能指标二尖瓣口血流频谱E峰、A峰、E/A比值,同时观察休息时肱动脉反应性充血后内径变化率。结果:单/双支病变组(第一组)E峰、E/A比值下降,肱动脉反应性充血后内径变化率低于正常对照组(P<0.05);三支病变组(第二组)E峰、E/A值无明显改变,肱动脉反应性充血后内径变化率明显低于对照组(P<0.01)。结论:肱动脉内皮依赖性舒张功能可作为鉴别冠心病左室舒张功能假性正常的指标。     

Role of natriuretic peptides in regulation of conduit artery distensibility

Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.