Involvement of the nitric oxide/L-arginine and sympathetic nervous systems on the vasodepressor action of human urotensin II in anesthetized rats.
This study examined if the nitric oxide (NO)/L-arginine pathway participates in and if the sympathetic nervous system attenuates the depressor action of human urotensin II. I.V. bolus injections of human urotensin II (0.1-30 nmol/kg) caused dose-dependent decreases in mean arterial pressure (MAP, EC(50) = 2.09 +/- 0.8 nmol/kg; Emax = -18 +/- 3 mmHg ) and increases in heart rate. The depressor response to human urotensin II (3 nmol/kg) was attenuated by approximately 50% in rats with MAP elevated through pretreatment with N(G)-nitro-L-arginine methyl ester (inhibitor of NO synthase), relative to that in rats with MAP elevated to a similar level through a continuous infusion of noradrenaline. Autonomic blockade with i.v. injections of mecamylamine (ganglion blocker) and propranolol (beta-adrenoceptor antagonist) markedly augmented the depressor response to human urotensin II, but almost completely attenuated the tachycardia. The results suggest that the depressor response to human urotensin II is partially mediated via the NO/L-arginine pathway, and is suppressed by activity of the sympathetic nervous system. Furthermore, tachycardic response to human urotensin II is primarily mediated indirectly via baroreflex mechanisms.
Abdelrahman
Aly M
AM
Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.
Pang
Catherine C Y
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*; D014579:Urotensins / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018733:Nicotinic Antagonists; D014579:Urotensins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D008464:Mecamylamine; C029677:urotensin II; D001120:Arginine; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine