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(Hypertension. 2007;49:170.)
© 2007 American Heart Association, Inc.

Original Articles

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Alfredo Gamboa; Cyndya Shibao; André Diedrich; Leena Choi; Bojan Pohar; Jens Jordan; Sachin Paranjape; Ginnie Farley; Italo Biaggioni

From the Departments of Medicine (A.G., A.D., B.P., S.P., G.F., I.B.) and Biostatistics (L.C.), Vanderbilt University, Nashville, Tenn; and Clinical Research Center (J.J.), Franz Volhard Clinic, Berlin, Germany.

Correspondence to Italo Biaggioni, 1500 21st Ave South, Suite 3500, Vanderbilt University, Nashville, TN 37212. E-mail italo.biaggioni{at}vanderbilt.edu

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^G-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<0.005). Thus, we report a novel approach to preferentially evaluate the role of eNO on BP control in normal and disease states. Our results suggest that eNO is one of the most potent metabolic determinants of BP in humans, tonically restraining it by 30 mm Hg.

Key Words: baroreflex • trimethaphan • phenylephrine • nitric oxide synthase • L-NMMA

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