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Analysis of the vasoconstrictor responses to potassium depolarization and norepinephrine and their antagonism by differing classes of vasodilators in the perfused rat hindquarters

EJ Sybertz, G Vander Vliet and T Baum

Although the role of calcium in activation of vascular smooth muscle has received considerable attention, few studies have analyzed responses of resistance vessels. We therefore evaluated the role of calcium in vasoconstriction induced by norepinephrine (NE) and by high potassium depolarization in the resistance vessels of the Krebs'- perfused rat hindquarters. In addition, responses to vasodilators of differing classes were assessed. Injection of NE (0.3-100 micrograms) into the hindquarters increased perfusion pressure in a dose-related manner. Perfusion of the hindquarters with a depolarizing salt solution (80 mM K+) produced a sustained vasoconstriction (perfusion pressure = 143 +/- 4 mm Hg). Vasoconstriction to NE and high K+ was abolished during perfusion with a Ca-free salt solution containing 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. In addition, the potassium-induced vasoconstriction was slightly reduced (perfusion pressure = 119 +/- 4 mm Hg) in animals pretreated with reserpine (5 mg/kg i.p.) indicating a slight neurogenic contribution to the response. The calcium channel blockers nifedipine (0.03-10 micrograms), diltiazem (0.3-30 micrograms) and verapamil (0.1-10 micrograms) produced dose-related vasodilation of hindquarters constricted with either NE (7.1 microM) or high potassium. These drugs were 4 to 10-fold more potent against potassium-induced vasoconstriction. Reserpine pretreatment enhanced the vasodilator response to nifedipine in potassium-depolarized preparations. Nitroprusside and nitroglycerin relaxed both NE and potassium-constricted hindquarters. The calmodulin blockers trifluoperazine and W-7 likewise produced vasodilation; trifluoperazine being 12.5 times more potent against NE-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 227, Issue 3, pp. 621-626, 12/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics







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 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics.