Altered .BETA.-Adrenoceptor-Mediated Responses in the Gastric Smooth Muscle of Hypertensive Rats.

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Effects of isoproterenol on contraction and membrane potential of gastric smooth muscle were studied in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Circular muscle preparation from the gastric fundus developed tonic contraction by re-administration of Ca2+ to a nominally Ca2+-free solution. The contraction was inhibited by nifedipine or nicardipine. Isoproterenol induced relaxation when it was applied to the Ca2+-induced contraction. The amplitude of isoproterenol-induced relaxation was concentration-dependent. Propranolol 10-6M abolished the relaxation induced by isoproterenol 10-7M. In the preparation from SHRSP, the amplitude of isoproterenol-induced relaxation was smaller than that from WKY between 3×10-9 and 10-7M. Forskolin, an adenylate cyclase activator, induced concentration-dependent relaxation. There was no difference in the relaxation induced by forskolin between preparations from WKY and SHRSP. Dibutilyl cyclic AMP, a membrane permeable analogue of cyclic AMP, also induced similar relaxation in preparations from WKY and SHRSP. Resting membrane potential of smooth muscle cell was not different between preparations from WKY and SHRSP. Isoproterenol hyperpolarized the membrane concentration-dependently. Isoproterenol-induced hyperpolarization in the preparation from SHRSP was smaller than that from WKY between 10-8 and 10-6M. When the membrane was depolarized by Tyrode’s solution containing 40mM K+, isoproterenol-induced hyperpolarization was almost abolished. In this condition, the isoproterenol-induced relaxation was inhibited partly, however, there was no difference in the amplitude of relaxation between preparations from WKY and SHRSP. Therefore, isoproterenol-induced hyperpolarization contributed at least partly to the relaxation. Forskolin hyperpolarized the membrane by the same amplitude in the preparations from WKY and SHRSP. These results indicate that a decrease in hyperpolarization may contribute to the decreased relaxation by isoproterenol in the preparation from SHRSP.

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