Sympathetic activation and nitric oxide function in early hypertension

Abstract

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...

Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity

“…The P values were generated by Mann-Whitney U-test. agreement as to whether LF SBP reflects sympathetic modulation of vascular tone (18,39,40,49), we have previously shown that LF SBP is increased in obese hypertensives (19,20,52), decreased in patients with pure autonomic failure, virtually abolished by autonomic ganglionic blockade (10,20,52), and was also greatly reduced in the patients with DBH deficiency included in this study. Furthermore, during orthostatic stress and the Valsalva maneuver, lean POTS had excessive HR responses, and higher BP and upright plasma norepinephrine levels, indicating recurrent episodes of excessive sympathetic activation whenever patients stood.…”

Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease

“…In the present study, the association between eNOS gene polymorphism and the risk of LCPD was analyzed in children from the Guangxi province of China, and it was found that the frequency of an a allele and ab genotype in intron 4 and allele 894T, GT genotype in exon 7 were significantly higher in patients with LCPD than in healthy controls. NO, synthesized by eNOS, has various roles in the vasculature, which include the regulation of vascular tone and blood pressure via vasodilation (26). NO also been suggested to be involved in the modulation of angiogenesis (27).…”

Baroreceptor stimulation enhanced nitric oxide vasodilator responsiveness, a new aspect of baroreflex physiology

“…Enhanced coupling between baroreflex and NO function may trigger a cascade of important cardiovascular regulatory mechanisms affecting global hemodynamics. It is plausible that arterial baroreflex inhibiting intrinsic fluctuations in sympathetic outflow dynamically sensitize vascular smooth muscle cells to NO, potentiating NO tonic restraint on blood pressure (Gamboa et al, 2012) and the blood pressure buffering system that rely on enhanced NO production and vasodilation in response to endothelial shear stress (Stauss and Persson, 2000). On microcirculatory level the same mechanism, linking , doses of sodium nitroprusside and phenylephrine (μg kg −1 ), respectively, given by intravenous bolus injection for BRS testing.…”

“…The amplification of vascular smooth muscle cell sensitivity to NO is suggested to be a new mechanism in baroreflex physiology, which can promote interactions between the sympathetic nervous system and NO function (Gamboa et al, 2012), regenerating reduced NO bioavailability, a crucial mechanism of microvascular and endothelial dysfunction (Kim et al, 2006;Napoli et al, 2006). The failure of this regulatory mechanism may establish important etiopathogenetic significance in coronary heart disease, arterial hypertension, insulin resistance and diabetes for which NO deficit and baroreflex dysfunction suggested to be a key feature and causing factor, importantly appearing in preclinical stages of the disease (Iellamo et al, 2006;Lesniewski et al, 2008).…”