Reduction of the pressor response to nicotine in the guinea pigs by a histamine (H3) agonist is attenuated by an inhibitor of nitric oxide synthesis.
We examined whether a histamine (H3)-agonist, (R) alpha-methylhistamine, [(R) alpha-MeHA] reduced the pressor responses induced by nicotine in urethane-anesthetized guinea pigs treated by atropine. Nicotine dose-dependently increased the basal mean arterial pressure (MAP) and the heart rate (HR) of the preparation. Both effects were due to stimulation of sympathetic ganglia, since muscarinic receptors were blocked. Adrenalectomy did not affect either the hypertension or the tachycardia to nicotine. Nicotine (7 micrograms kg-1) evoked a transient hypertension of approximately 30 mm Hg and a tachycardia by approximately 20 beats/min. (R) alpha-MeHA dose-dependently inhibited the increase in mean arterial pressure and the increase in HR to nicotine but not those produced by exogenous norepinephrine (NE). The inhibitory effects of (R) alpha-MeHA were dose-dependently antagonized by the H3-antagonist thioperamide, but not by combined mepyramine/cimetidine. They were also suppressed by a nitric oxide (NO)-synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME); this suppression was reversed by L-arginine. Histamine in the presence of mepyramine and cimetidine induced a similar inhibition of the hypertension to nicotine but a less potent inhibition of the tachycardia. These findings indicate that postganglionic noradrenergic nerve fibers are endowed with presynaptic H3-receptors, the stimulation of which inhibits NE release through an NO mechanism.
Ea-Kim
L
L
Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France.
Javellaud
J
J
Oudart
N
N
D000315:Adrenalectomy; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002927:Cimetidine / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D009538:Nicotine; D002927:Cimetidine; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; C052075:thioperamide; D019331:NG-Nitroarginine Methyl Ester