title: Contribution of endothelial nitric oxide to blood pressure in humans.
abstract: 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 approximately 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 microg/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 approximately 30 mm Hg.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.forename: Cyndya
authors.initials: C
authors.lastname: Shibao
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Leena
authors.initials: L
authors.lastname: Choi
authors.forename: Bojan
authors.initials: B
authors.lastname: Pohar
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
authors.forename: Sachin
authors.initials: S
authors.lastname: Paranjape
authors.forename: Ginnie
authors.initials: G
authors.lastname: Farley
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects; D003971:Diastole; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D012146:Rest; D012907:Smoking; D013599:Systole; D014294:Trimethaphan / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D014294:Trimethaphan; D052250:Nitric Oxide Synthase Type III