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(ω)-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 ± 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 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 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.

• Authors: Alfredo Gamboa, Luis E Okamoto, André Diedrich, Leena Choi, David Robertson, Ginnie Farley, Sachin Paranjape, Italo Biaggioni
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 302 Issue 7 Pg. H1438-43 (Apr 01 2012) ISSN: 1522-1539 [Electronic] United States
• PMID: 22287587 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Enzyme Inhibitors
• Nicotinic Antagonists
• Receptors, Nicotinic
• omega-N-Methylarginine
• Nitric Oxide
• Trimethaphan
• Nitric Oxide Synthase Type III

Topics

• Adolescent
• Adult
• Aging (physiology)
• Baroreflex (drug effects)
• Blood Pressure (drug effects, physiology)
• Enzyme Inhibitors (pharmacology)
• Female
• Heart Rate (drug effects)
• Humans
• Hypertension (physiopathology)
• Male
• Middle Aged
• Muscle Tonus (drug effects, physiology)
• Muscle, Smooth, Vascular (drug effects, physiology)
• Nicotinic Antagonists (pharmacology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type III (antagonists & inhibitors)
• Receptors, Nicotinic (drug effects)
• Smoking (physiopathology)
• Sympathetic Nervous System (drug effects, physiopathology)
• Trimethaphan (pharmacology)
• Young Adult
• omega-N-Methylarginine (pharmacology)