Nitric oxide modulates arteriolar responses to increased sympathetic nerve activity

Nase, G. P.; Boegehold, M. A.

doi:10.1152/ajpheart.1996.271.3.h860

Cited by 26 publications

(39 citation statements)

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“…Additional factors associated with early exercise hyperemia that affect adrenergic neurovascular function may include adenosine, potassium, endothelial-derived nitric oxide, and acetylcholine (20,26). Of these, nitric oxide, but not acetylcholine, was observed to contribute in a small but significant manner to the total hyperemic response after a single contraction (2), possibly through inhibition of sympathetic vasoconstriction (6).…”

Section: Discussionmentioning

confidence: 99%

Evidence for sympatholysis at the onset of forearm exercise

DeLorey

Wang

Shoemaker

2002

Journal of Applied Physiology

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The effect of augmented sympathetic outflow on forearm vascular conductance after single handgrip contractions of graded intensity was examined to determine whether sympatholysis occurs early in exercise (n ϭ 7). While supine, subjects performed contractions that were 1 s in duration and 15, 30, and 60% of maximal voluntary contraction (MVC) in intensity. The contractions were repeated during control and lower body negative pressure (LBNP) (Ϫ40 mmHg) sessions. Forearm blood flow (FBF; Doppler ultrasound) and mean arterial pressure were measured continuously for 30 s before and 60 s after the single contractions. Vascular conductance (VC) was calculated. Total postcontraction blood flow increased in an exercise intensity-dependent manner. Compared with control, LBNP caused a reduction in baseline and postexercise FBF (P Ͻ 0.05), VC (P Ͻ 0.01), as well as total excess flow (P Ͻ 0.01). Specifically, during LBNP, baseline FBF and VC were reduced by 29 and 34% of control, respectively (P Ͻ 0.05). After the 15% MVC contraction, peak VC during LBNP was reduced by a magnitude similar to that during baseline (i.e., ϳ30%), but it was only reduced by 15% during both the 30 and 60% MVC trials (P Ͻ 0.01). It was concluded that the stimuli for exercise hyperemia during moderate and heavy, but not mild, handgrip exercise intensities, diminish the vasoconstrictor effects of LBNP. Furthermore, these data demonstrate that this sympatholysis occurs early in exercise. Doppler ultrasound; forearm blood flow; vascular conductance; lower body negative pressure; sympathetic nervous system DESPITE CONSIDERABLE RESEARCH, the mechanisms responsible for the control of muscle blood flow at the onset of exercise remain elusive. Vascular tone at rest and during exercise is determined by the ability of vascular smooth muscle to integrate competing vasodilatory and vasoconstrictor signals from endothelial, metabolic, and neurogenic sources. At the onset of exercise, the early increase in muscle blood flow has been attributed to the muscle pump and an early rapid vasodilation (8,28,33). However, attempts to identify the substance(s) responsible for this early vasodilation have not been successful (34), and thus the search for an alternative explanation is warranted. The ability of the sympathetic nervous system to restrain blood flow to active skeletal muscle has been an active area of investigation. Several studies have demonstrated that there is sympathetic vasoconstriction in active skeletal muscle (4,14,21,22,27), and OЈLeary et al. (21) have argued that sympathetic activity directed to active skeletal muscle increases as exercise intensity increases.Conversely, other investigations have demonstrated an attenuation of vasoconstriction in active skeletal muscle during exercise (5, 24). This diminished vascular responsiveness to sympathetic stimulation was termed "sympatholysis" by Remensnyder et al. (24). Prejunctional inhibition of neurotransmitter release from the nerve terminal or an attenuation of postjunctional adrenergic-receptor respon...

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Section: Discussionmentioning

confidence: 99%

Evidence for sympatholysis at the onset of forearm exercise

DeLorey

Wang

Shoemaker

2002

Journal of Applied Physiology

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“…Although this is a valid technique, it is only useful as an acute indicator of sympathetic involvement, and one limitation of this method is that it is not possible to differentiate the effects of sympathetic nerve activity blockade on different vascular beds. It has been shown before that chronic blockade of NO may increase the vascular response to sympathetic activation (23). However, it is not possible to discriminate between a possible increase in vascular reactivity to catecholamines and an increase in the central activation of the SNS with the ganglionic blockade.…”

Section: Vc Biancardi Et Almentioning

confidence: 98%

Sympathetic activation in rats with L-NAME-induced hypertension

Biancardi

Bergamaschi

Lopes

et al. 2007

Braz J Med Biol Res

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We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/ kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means ± SEM) 2.47 ± 0.08 to 2.14 ± 0.07; conscious, 7 days: from 2.85 ± 0.13 to 2.07 ± 0.33; anesthetized, 2 days: from 3.00 ± 0.09 to 1.83 ± 0.25 and anesthetized, 7 days: from 3.56 ± 0.11 to 1.53 ± 0.10 mmHg mL -1 min -1 ) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 ± 4.5 to 96 ± 4; anesthetized: from 118 ± 1.5 to 104 ± 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.

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“…While there are multiple reports that alterations to adrenergic signaling are a major contributor to phenylephrineinduced (constrictor) responses (6,10,41,52), there is also considerable evidence in the existing literature that the impairments to endothelial function result in the loss of a "buffering" of adrenergic responses, such that these are enhanced independent from any changes to adrenergic signaling per se (29,42,43). Myogenic activation tended to be mildly increased with conditions of elevated PVD risk that included hypertension, potentially for a protective effect on the downstream microcirculation (14,59).…”

Section: H496mentioning

confidence: 99%

“…While certainly some of these effects are the result of the changes to endothelial function impacting the constrictor responses (29,42,43), there is previous evidence to support increases in adrenergic activity (6), receptor sensitivity (52), or downstream signaling gain (41) as potential contributors to increased constrictor responses in many of these models. While this would potentially reduce attractor variability further and would represent an additional, and possibly extremely robust, depressor of arteriolar function and flexibility in the control of tissue perfusion, it is unclear that a simple "increase in adrenergic constrictor reactivity" accurately represents the prevailing condition in conditions of elevated PVD risk that are associated with obesity and hypertension (28,30,37).…”

Section: H499mentioning

confidence: 99%

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

Frisbee

Butcher

Frisbee

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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-To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning "healthy" to "high PVD risk" and used a multiscale approach to interrogate microvascular function and outcomes: healthy: SpragueDawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A 2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. rodent models of cardiovascular disease risk; peripheral vascular disease; blood flow regulation; microvascular dysfunction; system biology of microcirculation NEW & NOTEWORTHY Linking peripheral vascular disease (PVD) risk to integrated microvascular dysfunction and health outcomes has been elusive. We used eight models of increasing risk and a multiscale approach to interrogate novel indexes of microvascular function, perfusion/oxygen handling, and outcomes. We demonstrate how elevated PVD risk leads to progressive microvascular "dampening," with clear implications for outcomes.THE PREDOMINANT CONCERN regarding the presence of peripheral vascular disease (PVD) risk factors of increasing severity is that these can lead to the development of pathological characteristics of PVD including myocardial infarction, heart failure, stoke, and/or limb ischemia. These potential outcomes of PVD result in elevations in mortality risk as well as significant reductions in quality of life through a variety of direct and indirect causes (3,45,50) that are predominantly perceived as macrovascular events. These global processes can develop across tissues and organs, leading to the clinica...

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Nitric oxide modulates arteriolar responses to increased sympathetic nerve activity

Cited by 26 publications

References 0 publications

Evidence for sympatholysis at the onset of forearm exercise

Evidence for sympatholysis at the onset of forearm exercise

Sympathetic activation in rats with L-NAME-induced hypertension

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

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