Mode of action of pinacidil and its analogs P1060 and P1368: results of studies in rat blood vessels

Journal Article · Fri Jan 01 04:00:00 EST 1988 · J. Cardiovasc. Pharmacol.; (United States)

DOI:https://doi.org/10.1097/00005344-198812002-00004· OSTI ID:6326977

Weston, A H; Southerton, J S; Bray, K M; Newgreen, D T; Taylor, S G

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.

• Research Organization: Manchester Univ. Medical School (England)
• OSTI ID: 6326977
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States); ISSN JCPCD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL ISOTOPES
ANIMALS
AORTA
ARTERIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MARKERS
BIOLOGICAL PATHWAYS
BLOOD VESSELS
BODY
CARBONIC ACID DERIVATIVES
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
CONTRACTION
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTROPHYSIOLOGY
GUANIDINES
IN VITRO
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANES
MINUTES LIVING RADIOISOTOPES
MUSCLES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHYSIOLOGY
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
TRACER TECHNIQUES
VASODILATORS
VEINS
VERTEBRATES