The mode of action of pinacidil and its analogs P1060 and P1368: results of studies in rat blood vessels
| Autor: | Arthur H. Weston, D. T. Newgreen, S.G. Taylor, J. S. Southerton, K.M. Bray |
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| Rok vydání: | 1988 |
| Předmět: |
Male
Contraction (grammar) Vasodilator Agents Vasodilation Aorta Thoracic Pharmacology In Vitro Techniques Guanidines Muscle Smooth Vascular Membrane Potentials chemistry.chemical_compound medicine.artery medicine Animals Aorta Chemistry Portal Vein Pinacidil Rats Inbred Strains Smooth muscle contraction Hyperpolarization (biology) musculoskeletal system Rats Electrophysiology Biochemistry Cardiovascular agent cardiovascular system Cardiology and Cardiovascular Medicine Microelectrodes Rubidium Radioisotopes Muscle Contraction |
| Zdroj: | Journal of cardiovascular pharmacology. 12 |
| ISSN: | 0160-2446 |
| Popis: | In rat portal vein and aorta, pinacidil (0.3-100 microM) inhibited spontaneous mechanical activity (portal vein) and responses to norepinephrine (0.001-100 microM) and to KCl (5-80 mM). Pinacidil and its analogs P1060 and P1368 inhibited established contractions to 20 mM KCl but had little effect on responses to 80 mM KCl. The order of spasmolytic potency was P1060 greater than pinacdil greater than P1368. Intracellular electrical recording showed that in a portal vein, pinacidil (0.3-10 microM) abolished spontaneous electrical activity and hyperpolarized the cells to the region of the calculated EK. Pinacidil (3-10 microM) produced a similar hyperpolarization in rat aorta, and in both tissues the hyperpolarization was maintained in the continuing presence of pinacidil. Using /sup 86/Rb as a K+ marker, pinacidil increased /sup 86/Rb exchange in both the rat portal vein and aorta. The analog P1060 also increased /sup 86/Rb efflux in the rat portal vein; P1368 had no significant effect. It is concluded that the inhibitory effects of pinacidil in rat blood vessels are associated with the opening of /sup 86/Rb-permeable K+ channels. This mechanism produces a low-resistance pathway in the membrane and this inhibits the ability of pressor agents to produce smooth muscle contraction. |
| Databáze: | OpenAIRE |
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