Enhancement of muscle blood cell flux and pO2 by cromakalim (BRL 34915) and other compounds enhancing membrane K+ conductance, but not by Ca2+ antagonists or hydralazine, in an animal model of occlusive arterial disease.
The effect of Ca2+ antagonists, hydralazine and agents which enhance membrane K+ conductance (cromakalim, pinacidil and nicorandil) in smooth muscle cells, was compared on normal and hypoxic skeletal muscle blood cell flux and pO2. The K+ conductance enhancers and verapamil, diltiazem and nifedipine increased blood cell flux in normally perfused muscle. At equieffective blood pressure lowering dosages, the Ca2+ antagonists produced greater increases than the K+ channel openers. Hydralazine did not elevate blood cell flux in the normal muscle. In hypoxic skeletal muscle, the K+ conductance enhancers produced a marked increase in blood cell flux and in tissue oxygen tension, indicating that they had increased the nutritive blood flow in the muscle. The Ca2+ antagonists and hydralazine either did not change hypoxic muscle blood cell flux and pO2 or reduced them. The dissimilarity in the activity of the compounds may be due to differences in their site of action in the vascular bed. Ca2+ antagonists and hydralazine are known to reduce arteriolar vessel resistance and do not increase blood flow in hypoxic skeletal muscle. The positive effect of cromakalim, pinacidil and nicorandil may be due to relaxant activity on larger arterial blood vessels including collaterals. This effect could be related to their ability to enhance membrane K+ conductance in vascular smooth muscle cells.
Angerbach
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D
Beecham-Wülfing Research Laboratories, Gronau, Federal Republic of Germany.
Nicholson
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CD
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001578:Benzopyrans / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019806:Cromakalim; D006830:Hydralazine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects
D000959:Antihypertensive Agents; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D011758:Pyrroles; D019806:Cromakalim; D006830:Hydralazine; D011188:Potassium