Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2007-01, Vol.49 (1), p.170-177
• Main Authors: Gamboa, Alfredo, Shibao, Cyndya, Diedrich, André, Choi, Leena, Pohar, Bojan, Jordan, Jens, Paranjape, Sachin, Farley, Ginnie, Biaggioni, Italo
• Format: Article
• Language: English
• Subjects: Adult; Arterial hypertension. Arterial hypotension; Autonomic Nervous System - drug effects; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Blood vessels and receptors; Cardiology. Vascular system; Cardiotonic Agents - pharmacology; Cardiovascular System - drug effects; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Diastole; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Ganglionic Blockers - pharmacology; Humans; Male; Medical sciences; Nitric Oxide Synthase Type III - drug effects; Nitric Oxide Synthase Type III - physiology; omega-N-Methylarginine - pharmacology; Phenylephrine - pharmacology; Rest; Smoking; Systole; Trimethaphan - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/01.HYP.0000252425.06216.26

Impaired endothelial-derived NO (eNO) is invoked in the development of many pathological conditions. Systemic inhibition of NO synthesis, used to assess the importance of NO to blood pressure (BP) regulation, increases BP by ≈15 mm Hg. This approach underestimates the importance of eNO, because BP is restrained by baroreflex mechanisms and does not account for a role of neurally derived NO. To overcome these limitations, we induced complete autonomic blockade with trimethaphan in 17 normotensive healthy control subjects to eliminate baroreflex mechanisms and contribution of neurally derived NO. Under these conditions, the increase in BP reflects mostly blockade of tonic eNO. N-Monomethyl-l-arginine (250 μg/kg per minute IV) increased mean BP by 6±3.7 mm Hg (from 77 to 82 mm Hg) in intact subjects and by 21±8.4 mm Hg (from 75 to 96 mm Hg) during autonomic blockade. We did not find a significant contribution of neurally derived NO to BP regulation after accounting for baroreflex buffering. To further validate this approach, we compared the effect of NOS inhibition during autonomic blockade in 10 normotensive individuals with that of 6 normotensive smokers known to have endothelial dysfunction but who were otherwise normal. As expected, normotensive smokers showed a significantly lower increase in systolic BP during selective eNO blockade (11±4.5 versus 30±2.3 mm Hg in normotensive individuals; P