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Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition
Author(s) -
Puscas Ioan,
Gilau Ludovic,
Coltau Marcela,
Pasca Radu,
Domuta Gabriela,
Baican Michael,
Hecht Alex
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.110559
Subject(s) - verapamil , carbonic anhydrase , amlodipine , chemistry , pharmacology , mechanism of action , acetazolamide , calcium channel , calcium , calcium channel blocker , in vivo , vascular smooth muscle , blood pressure , in vitro , endocrinology , medicine , enzyme , biochemistry , smooth muscle , biology , microbiology and biotechnology , organic chemistry
In this article we studied in vitro and in vivo the effect of calcium channel blockers (verapamil and amlodipine) on erythrocyte carbonic anhydrase I activity, on carbonic anhydrase I isolated from vascular smooth muscles, and on arterial blood pressure values in human beings and in animals. Our in vitro and in vivo results have shown that verapamil and amlodipine are strong inhibitors of carbonic anhydrase I both in erythrocytes (in human beings) and in vascular smooth muscles (in animals). In human beings calcium channel blockers reduce arterial blood pressure in subjects with hypertension and progressively reduce erythrocyte carbonic anhydrase I activity. We assume that verapamil and amlodipine possess a dual mechanism of action: the first mechanism consists of their action on calcium channels, and the second mechanism, proposed by us, shows that verapamil and amlodipine inhibit vascular smooth muscle carbonic anhydrase I activity with consecutive pH increase. The increase of pH might be an additional factor involved in intracellular calcium influx through calcium channels. This dual mechanism of action would bring new data regarding the hypotensive effect of verapamil and amlodipine, effects that might also be parallel and dependent on carbonic anhydrase I inhibition. (Clin Pharmacol Ther 2000;68:443‐9.) Clinical Pharmacology & Therapeutics (2000) 68 , 443–449; doi: 10.1067/mcp.2000.110559