Cardiovascular and Sympathetic Effects of Nitric Oxide Inhibition at Rest and During Static Exercise in Humans

Owlya, Reza; Vollenweider, L; Trueb, Lionel; Sartori, Cláudio; Lepori, Mattia; Nicod, Pascal; Scherrer, Urs

doi:10.1161/01.cir.96.11.3897

Cited by 95 publications

(83 citation statements)

References 30 publications

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“…In some studies, the increase in BP produced by systemic administration of L-NMMA is accompanied by a similar reflex decrease in muscle sympathetic nerve activity to that produced by an equipressor dose of phenylephrine (3,8), suggesting that NO does not tonically restrain central sympathetic outflow in humans. Other studies have reached the opposite conclusion; in one study, NOS inhibition increased BP but did not produce the expected baroreflex-mediated decrease in sympathetic nerve activity (15); in another, the increase in BP induced by NOS inhibition was partially reversed by the ␣-adrenergic antagonist phentolamine (21). These results suggest that the pressor response to systemic NOS inhibition is at least in part mediated by sympathetic activation, implying tonic inhibition of the sympathetic nervous system by NO.…”

Section: Discussionmentioning

confidence: 93%

Sympathetic activation and nitric oxide function in early hypertension

Gamboa

Okamoto²,

Diedrich³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with N -monomethyl-L-arginine (L-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to L-NMMA. We enrolled a total of 66 subjects (39 Ϯ 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as "positive" controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, L-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 Ϯ 2, 32 Ϯ 2, and 30 Ϯ 3 mmHg, respectively), whereas the response of smokers was blunted (16 Ϯ 5 mmHg, P ϭ 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ϳ30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study.hypertension; nitric oxide; nervous system; autonomic; nervous system; sympathetic; nitric oxide synthase NITRIC OXIDE (NO) is arguably the most important metabolic modulator of blood pressure (BP); our previous studies suggest that NO tonically restrains BP by at least 30 mmHg in healthy young adults (6). Not surprisingly, there has been great interest in determining if impaired NO function plays a role in hypertension. Reduced NO production (5) or bioavailability (1), or impaired NO-mediated vasodilation (17), have been implicated in the development or maintenance of hypertension (2). There is, indeed, significant evidence that NO function is impaired in hypertension, but the precise mechanism underlying this problem is less clear. There are at least two mechanisms by which NO can lower BP. NO, derived from endothelial cells or from nitrergic nerves, tonically produces vasodilatation. NO also interacts with the sympathetic nervous system at multiple levels and, through this interaction, can modulate BP. In particular, several lines of evidence suggest that NO tonically suppresses sympathetic tone (22,31), and impaired NO function could contribute to the sympathetic activation observed in hypertension. Conversely, sympathetic activation can impair NO function (9). It is possible, therefore, that these interactions between NO and the symp...

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Section: Discussionmentioning

confidence: 93%

Sympathetic activation and nitric oxide function in early hypertension

Gamboa

Okamoto²,

Diedrich³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…47) For example, the neurotransmitter dopamine is a potent regulator of important signaling insuffi cient to cause dysfunction, and the ANS pathway was considered to be critical for the development of the pathologic process of hypertension. 28) In addition to endothelial function, other vascular functions were reported to be correlated with the state of the ANS. Yeragani, et al compared vascular indices and heart rate and QT variability measures in patients with anxiety disorders.…”

Section: Neurogenic Factor-mediated Pathway To the Endotheliummentioning

confidence: 99%

The Relationship between Vascular Function and the Autonomic Nervous System

Amiya

Watanabe

Komuro

2014

Annals of Vascular Diseases

106

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Endothelial dysfunction and autonomic nervous system dysfunction are both risk factors for atherosclerosis. There is evidence demonstrating that there is a close interrelationship between these two systems. In hypertension, endothelial dysfunction affects the pathologic process through autonomic nervous pathways, and the pathophysiological process of autonomic neuropathy in diabetes mellitus is closely related with vascular function. However, detailed mechanisms of this interrelationship have not been clearly explained. In this review, we summarize fi ndings concerning the interrelationship between vascular function and the autonomic nervous system from both experimental and clinical studies. The clarifi cation of this interrelationship may provide more comprehensive risk stratifi cation and a new effective therapeutic strategy against atherosclerosis.

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“…Endothelial dysfunction characterizes arterial hypertension, and pharmacological blockade of eNOS by L-NMMA raises blood pressure (Owlya et al 1997), so diminished NO availability is a plausible mechanism to link As with hypertension (Hsueh et al 2005). Moreover, As decreases in vitro vascular relaxation capability, both endothelium-dependent and endothelium-independent, directly acting on the smooth muscle cells (Lee et al 2003), while it potentiates response to vasoconstrictors through myosin light chain phosphorylation and Ca ++ sensitization/inflow (Lee et al 2005;Li et al 2010;Lim et al 2011).…”

Section: Other Mechanisms Of CV Damagementioning

confidence: 99%