Effects of calcium antagonists on mean circulatory filling pressure in the conscious rat.
The effects of three calcium antagonists (verapamil, nifedipine, and flunarizine) on mean arterial pressure (MAP), heart rate (HR), and mean circulatory filling pressure (MCFP), an index of total body venous tone, were investigated in the conscious, unrestrained rat. Infusions of all three drugs caused a dose-dependent decrease in MAP and an increase in MCFP, compared with the corresponding values in control rats. HR was decreased by verapamil and flunarizine and slightly increased by nifedipine. Further experiments investigated whether the increase in MCFP by verapamil was indirectly caused by reflex activation of the sympathetic nervous system. Rats were pretreated with a continuous infusion of hexamethonium prior to the infusion of verapamil. After treatment with hexamethonium, verapamil did not increase the MCFP. In fact, the highest dose of verapamil significantly decreased MCFP. The results suggest that calcium antagonists have greater dilator effects in arterioles compared to veins. It appears that any direct venodilator effects of verapamil in conscious rats are masked due to reflex activation of the autonomic nervous system.
Waite
R P
RP
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
C C
CC
Walker
M J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006584:Hexamethonium Compounds; D014700:Verapamil; D005444:Flunarizine