Pilocarpine-induced relaxation of rat tail artery by a non-cholinergic mechanism and in the absence of an intact endothelium.
1. The partial muscarinic agonist, pilocarpine, evoked concentration-dependent relaxation with an EC50 of 2.4 x 10(-3) M in isolated segments of rat tail artery that were constricted with phenylephrine (10(-8) to 2 x 10(-7) M). Acetylcholine also evoked concentration-dependent relaxation but was more potent than pilocarpine (EC50, 6.5 x 10(-7) M). 2. The concentration-relaxation curves for pilocarpine were not affected by the muscarinic antagonists, atropine (10(-9) M) or pirenzepine (5 x 10(-7) M), while the concentration-relaxation curves for acetylcholine-evoked relaxation of the same tissues were shifted some 10 fold to the right by these concentrations of atropine and pirenzepine. 3. Acetylcholine failed to evoke relaxation following removal of the endothelium. The smooth muscle of the rat tail artery was some 10 fold more sensitive to the relaxing action of pilocarpine following denudation of the endothelium. 4. The effects of pilocarpine and acetylcholine on membrane potential were studied in tissues that were depolarized to -39 +/- 1 mV with phenylephrine (5 x 10(-8) to 2 x 10(-7) M). In intact tissues, pilocarpine caused hyperpolarization, an effect that persisted in the presence of muscarinic antagonists. Acetylcholine also evoked hyperpolarization. 5. Following removal of the endothelium, pilocarpine (10(-5) to 10(-3) M) evoked hyperpolarization in 6 of 15 preparations and a decrease in the frequency of action potentials in the remainder. Both of these responses were associated with relaxation. 6. The effects of pilocarpine were compared with other agents that evoke endothelium-independent relaxation. The concentration-relaxation curves in response to pilocarpine and nitroprusside were shifted to the right by ferricyanide (10-5 M) and methylene blue (10-5 M). Glibenclamide (10-6 M) was without effect on the hyperpolarization and relaxation evoked by pilocarpine (10' to 10- M).7. Thus, pilocarpine evokes relaxation of rat tail artery independently of the cholinergic system and it is suggested that this is achieved by decreasing the frequency of action potentials in the smooth muscle.
Tonta
M A
MA
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Parkington
H C
HC
Tare
M
M
Coleman
H A
HA
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001341:Autonomic Nervous System / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013623:Tail / Q000098:blood supply
D001578:Benzopyrans; D011758:Pyrroles; D010862:Pilocarpine; D019806:Cromakalim; D009599:Nitroprusside; D010656:Phenylephrine; D007545:Isoproterenol; D000109:Acetylcholine; D008751:Methylene Blue