Prolonged NOS inhibition in the brain elevates blood  pressure in normotensive rats

Sakima, Atsushi; Teruya, Hiroshi; Yamazato, Masanobu; Matayoshi, Rijiko; Muratani, Hiromi; Fukiyama, Koshiro

doi:10.1152/ajpregu.1998.275.2.r410

Cited by 11 publications

(8 citation statements)

References 24 publications

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“…Intracerebroventricular injection of L-NMMA, at doses that have no effect when given systemically, has been shown to increase sympathetic activity and BP (19,24). The hypotensive effect of the central sympatholytic dexmedetomidine is absent in endothelial nitric oxide synthase (eNOS) knockout mice, indicating that an intact eNOS system within the central nervous system is required for autonomic BP regulation.…”

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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“…administration of L-arginine lowers blood pressure and sympathetic activity in Wistar rats (27), whereas i.c.v. injection of L-NMMA has just the opposite effects (28). In addition, the absence of NO in L-NAME hypertensive rats increases the pressor effects of acute i.c.v.…”

Section: Fig 4 the Relationships Between Basal Map And Captopril-inmentioning

confidence: 97%

Antihypertensive Mechanisms of Chronic Captopril or N-Acetylcysteine Treatment in L-NAME Hypertensive Rats

2006

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“…Experiments with chronic inhibition of nNOS demonstrated that prolonged (over 3 weeks) inhibition of central nNOS is required before changes in the SAP become measurable. More and more studies suggest that the central NO system provides potent effects within periods of increased sympathetic activity but not within periods of the basal level of the latter [88].…”

Section: Pathophysiological Implications Of Nomentioning

confidence: 99%

Nitric oxide: Involvement in the nervous control of cardiovascular function

Shapoval

2004

Neurophysiology

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Identification of nitric oxide (NO) as a neurotransmitter in the CNS resulted in initiation of numerous studies aimed at elucidating the roles of NO not only at a cellular level, but also in regulation of the activity of specific physiological systems coordinated by the brain. In this lecture, we will discuss the state of current knowledge about cellular events in the brain realized with the involvement of NO, distribution of NO-producing neurons in cerebral structures providing central cardiovascular control, peculiarities of NO production, and mechanisms underlying NO-mediated neuromodulatory effects on cardiovascular function. Activation of the NO system in the lower brainstem modulates a variety of neuronal pathways; NO was shown to induce GABA and glutamate releases within the medulla. The NO system in the brain is activated in the states of homeostatic imbalance, including hypertension and stress.

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Prolonged NOS inhibition in the brain elevates blood pressure in normotensive rats

Cited by 11 publications

References 24 publications

Sympathetic activation and nitric oxide function in early hypertension

Sympathetic activation and nitric oxide function in early hypertension

Antihypertensive Mechanisms of Chronic Captopril or N-Acetylcysteine Treatment in L-NAME Hypertensive Rats

Nitric oxide: Involvement in the nervous control of cardiovascular function

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