The antihypertensive mechanism of verapamil. Alteration of glomerular filtration rate regulation.
The renal hemodynamic and renin release responses to verapamil were analyzed to determine if the antihypertensive action of the calcium entry blocker could be due to its renal effects. Hemodynamic and renin release measurements were compared in a control group of nine anesthetized rabbits and in a group of 10 rabbits given verapamil (200 micrograms/kg i.v. initially, 4 micrograms/kg/min thereafter), starting 30 minutes before data collection. Measurements were made over a range of controlled renal perfusion pressure from 100 to 40 mm Hg. The renal blood flow at 100 mm Hg of the verapamil-treated group was 18% greater (p less than 0.02) than that of the control group, while the glomerular filtration rate was 51% greater (p less than 0.001) than that of the control group. Renal blood flow and glomerular filtration rate autoregulation were highly effective in the control group down to 80 mm Hg, but both variables were poorly regulated in the verapamil-treated group. The filtration fraction of the treated group was 36.9 +/- 1.5% versus 28.5 +/- 1.6% in the control group (p less than 0.003) at 100 mm Hg, and the filtration fraction of the treated group remained significantly greater down to 40 mm Hg. Renin release rates of the two groups were similar at the 100 mm Hg pressure level, but the increase in release due to the progressive reduction in perfusion pressure was significantly greater in the treated group than in the control group. At the 80 mm Hg pressure level, the mean release rate for the treated group was more than three times greater (p less than 0.05) than that of the control group. These findings demonstrate that verapamil is an effective renal vasodilator and that the effect is proportionally greater on the preglomerular than on the postglomerular resistance. This action could be the basis for its antihypertensive efficacy.
Lin
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HB
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505.
Young
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DB
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D000959:Antihypertensive Agents; D014700:Verapamil