Sympathetically mediated hypertension caused by chronic inhibition of nitric oxide.
Pharmacological inhibition of nitric oxide synthase causes sustained hypertension in many animal species. Although this hypertension has been attributed to inhibition of endothelium-dependent vasodilation, short-term studies in anesthetized preparations have advanced the hypothesis that there could be a sympathetic component to this hypertension. To test this hypothesis we measured intra-arterial pressure directly before and after 1 week of treatment with the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, approximately 80 mg/kg per day in drinking water) in conscious unrestrained rats with or without chronic guanethidine-induced sympathectomy. The major new finding is that the hypertensive response to L-NAME was greatly attenuated by sympathectomy. With L-NAME, mean arterial pressure increased from 101 +/- 3 to 152 +/- 6 mm Hg in rats without sympathectomy (n = 11) but only from 96 +/- 2 to 122 +/- 3 mm Hg in rats with sympathectomy (n = 15, +52 +/- 5 versus +27 +/- 4 mm Hg, P < .01). Sympathectomy did not alter maximal endothelium-dependent vasodilation assessed by femoral vascular responses to intra-arterial acetylcholine or bradykinin, indicating that the differing hypertensive responses to L-NAME in rats with versus without sympathectomy could be related to inhibition of neuronal rather than endothelial nitric oxide synthesis. We also found that L-NAME-induced hypertension, once developed, is completely reversed by acute ganglionic blockade. In conclusion, these findings identify an important sympathetic neural component to the sustained hypertension produced by pharmacological inhibition of nitric oxide in the rat.
Sander
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8573, USA.
Hansen
P G
PG
Victor
R G
RG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006973:Hypertension / Q000209:etiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors
D009569:Nitric Oxide; D001120:Arginine; D002714:Chlorisondamine; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester