L-NAME raises systolic blood pressure in the pithed rat by a direct adrenal epinephrine releasing action.
It is generally thought that inhibition of nitric oxide synthase leads to blood pressure elevation largely through reduction in vascular levels of the vasodilator nitric oxide. However, there are several reports suggesting that NO synthase inhibitors cause adrenal epinephrine (E) release by both central and peripheral mechanisms. We investigated the role of adrenal E in the pressor effects of the nitric oxide synthase inhibitor L-NAME in the pithed rat to help distinguish central from peripherally mediated actions. L-NAME (10 mg/kg) raised both systolic and diastolic BP by about 30 mm Hg (P < .01) in the absence of exogenous electrical stimulation of sympathetic nerves. During stimulation at 10 V and frequencies of 1 or 2 Hz, systolic BP was about 70 mm Hg higher in L-NAME treated rats than in drug free stimulated rats. This enhancement of systolic BP by L-NAME was less pronounced at 5 or 10 Hz stimulation frequencies. Following these types of electrical stimulations of pithed rats, both plasma norepinephrine (NE) and E levels were dramatically elevated above resting plasma levels. L-NAME pretreatment of these electrically stimulated rats increased plasma E levels by an additional 60% and decreased NE by 18%. Acute adrenalectomy dramatically reduced plasma E levels and abolished the ability of L-NAME to enhance the pressor effect of sympathetic stimulation. In contrast, acute adrenalectomy of unstimulated pithed rats did not significantly reduce the pressor response to L-NAME. We conclude that adrenal E release may mediate much of the systolic pressor response of L-NAME in the stimulated pithed rat, but the magnitude of this effect varies with stimulation frequency. Since pithing disrupts central pathways, this induction of adrenal E release by L-NAME is a peripheral effect.
Elayan
Hamzeh H
HH
Faculty of Medicine, Jordan University, Amman, Jordan.
Kennedy
Brian P
BP
Ziegler
Michael G
MG
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D003655:Decerebrate State / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects; D014628:Vagotomy
D002395:Catecholamines; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine