Effects of neuropeptide Y on contraction, relaxation, and membrane potential of rabbit cerebral arteries.
The effects of porcine neuropeptide Y (NPY) on agonist-induced contraction, relaxation, and intracellular membrane potential were studied in isolated ring segments of rabbit cerebral arteries. NPY caused contraction of cerebral arteries with a mean EC50 of 2.7 +/- 0.07 nM. After exposure of cerebral arteries to 1.5 nM NPY, the potencies of norepinephrine (NE) and histamine in causing contraction were increased by approximately twofold, with no change in maximal contraction. In cerebral arteries contracted with histamine, adenosine, and acetylcholine-induced relaxation was inhibited by 7-14-fold in the presence of 1.5 nM NPY, with no change in maximal relaxation. These effects of NPY were not altered by sympathetic denervation of cerebral arteries. Intracellular membrane potential in smooth muscle cells of cerebral arteries was measured using glass microelectrodes and averaged -66 +/- 1 mV. NPY 3 nM, ouabain 3 microM, and K+ Krebs solution 1 mM depolarized cerebral arteries by 15, 22, and 14 mV, respectively. In arteries depolarized by ouabain or 1 mM K+ Krebs solution, 3 nM NPY caused no additional depolarization. The potency of NE in causing contraction of cerebral arteries was increased by 3 microM ouabain (3.8-fold) and 1 mM K+ Krebs solution (1.9-fold); however, 3 nM NPY in the presence of ouabain or 1 mM K+ Krebs solution caused no greater increase in agonist potency. Ouabain 3 microM inhibited adenosine-induced relaxation by 5.1-fold whereas addition of 3 nM NPY to ouabain exposed arteries caused an additional 4.6-fold inhibition of relaxation. Ouabain and ouabain plus NPY also decreased the maximal relaxant effect of adenosine. These results suggest that the ability of NPY to potentiate contraction and inhibit relaxation of cerebral arteries is caused, at least in part, by NPY-induced membrane depolarization.
Abel
P W
PW
Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska 68178.
Han
C
C
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D009478:Neuropeptide Y; D010042:Ouabain; D006632:Histamine; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium