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 of 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 μM, 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 μM 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 μM 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.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Cardiovascular Pharmacology|
|State||Published - Jan 1 1989|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine