The pressor effect of NO synthase inhibition correlates to pre-existing systolic BP in the rat.
A number of studies have found that the vasopressor effect of nitric oxide (NO) synthase inhibition is small following treatment with hypotensive agents but is enhanced after hypertensive agents, and have implicated NO in the mechanism of action of these drugs. We investigated the hypothesis that the rate of vascular NO synthesis is directly related to blood pressure. The vasopressor effect of 10 mg/kg of L-nitro-L-arginine methyl ester (L-NAME) was studied in relation to changes in BP induced by a variety of treatments in both pentobarbital sodium anesthetized and pithed rats. BP reductions were induced by blood withdrawal, surgery and pithing. BP increases were made by injecting 10 and 15 microg/kg boluses of phenylephrine or by injecting 5% albumin solution. Pithing decreased baseline BP and attenuated the vasopressor effect of L-NAME while phenylephrine increased both BP levels and the hypertensive effect of L-NAME. Volume expansion with 5% albumin solution increased both BP and the vasopressor effect of L-NAME. Both surgery (abdominal incision) and withdrawal of 1 ml blood reduced BP and attenuated the pressor effect of L-NAME. When the results of all these studies were combined, systolic BP was found to correlate strongly with the vasopressor effect of L-NAME (R2 = 0.73, P < 0.0001). Diastolic BP correlated less well with L-NAME (R2 = 0.36, P < 0.0003). The results suggest that shear stress generated by blood flow during the systole releases NO, and lowers BP. The pressor effect of NO synthase inhibition is closely related to pre-existing systolic BP.
Elayan
Hamzeh H
HH
Faculty of Medicine, Jordan University.
Kennedy
Brian P
BP
Ziegler
Michael G
MG
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D020896:Hypovolemia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013599:Systole / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000418:Albumins; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester