The Effect of Moxonidine on Endothelial Dysfunction in Metabolic Syndrome

Topal, Ergün; Cikim, Ayse Sertkaya; Cikim, Kerim; Temel, İsmail; Оздемир, Рамазан

doi:10.2165/00129784-200606050-00007

Cited by 37 publications

(25 citation statements)

References 36 publications

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“…For example, acute sympathetic activation blunts flow-mediated dilation (9), mimicking an "endothelial dysfunction state," and, conversely, the central sympatholytic moxonidine decreases sympathetic activity (30) and improves flow-mediated dilation (28). Thus, it is plausible that results from previous studies in hypertensive subjects do not reflect an intrinsic impairment of NO vasodilatation but a functional impairment secondary to increased sympathetic activity.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…37) In humans, ANS modulation by alpha2-adrenoreceptor agonists has also been shown to improve endothelial dysfunction in patients with hypertension. 38) These fi ndings suggest a contribution of sympathetic nervous tone on the baseline condition of vascular function. In addition, experimental data suggest that exaggerated sympathetic nervous activity modifi es other aspects of endothelial function, such as increasing the immunoreactivity of ECs, or promoting the uptake of low-density lipoprotein cholesterol by ECs.…”

Section: Correlations Between Impairments In the Ans And Endothelial mentioning

confidence: 94%

The Relationship between Vascular Function and the Autonomic Nervous System

Amiya

Watanabe

Komuro

2014

Annals of Vascular Diseases

101

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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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“…15 In human studies, autonomic nervous system modulation by α2-adrenoreceptor agonists has been shown to improve endothelial dysfunction in patients with hypertension. 16 In addition, experimental data suggest that exaggerated sympathetic nervous system activity increases the immunoreactivity of endothelial cells, or promotes the uptake of LDL by endothelial cells, which is another example of endothelial modulation by the autonomic nervous system. 17, 18 As regards the signaling route from the autonomic nervous system to endothelial cells, the autonomic nervous system is thought to signal the endothelial cell layer from the side of the adventitial autonomic nervous system, whereas most endothelium-damaging factors act from the endoluminal side.…”

Section: Mechanism Of Interaction Between Endothelial Function and Aumentioning

confidence: 99%