Effects of verapamil, nifedipine and flunarizine on haemodynamics and regional blood flows in pentobarbitone-anaesthetized rats.
Representative calcium antagonists from proposed class I (nifedipine), class II (verapamil) and class III (flunarizine) have been examined for effects on blood pressure, heart rate, ventricular pressures, ECG, cardiac output and regional blood flow in pentobarbitone-anaesthetized rats. Flow was measured by the microsphere technique. Low and high infusion rates of each drug were chosen to decrease mean arterial pressure by 25 and 40 mmHg, respectively. At equi-depressor infusion rates, all drugs equally decreased total peripheral resistance and slightly increased cardiac output and stroke volume. Heart rate was decreased by verapamil and flunarizine, but increased by nifedipine. Verapamil markedly decreased dP/dtmax of ventricular pressure and prolonged the PR-interval. Flunarizine was similar. Nifedipine decreased dP/dtmax and had no effect on the PR-interval of the ECG. Similar effects on regional blood flow were seen with the three drugs; flow to lungs, heart, liver, skeletal muscle and stomach increased. Correction for blood pressure changes, i.e. conductance, showed that vasodilatation occurred in all regions, with all drugs, except for the skin. Therefore, representatives from three sub-classes of calcium antagonists had similar effects on blood flow but different effects on the heart.
Waite
R P
RP
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
C C
CC
Walker
M J
MJ
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004562:Electrocardiography; D005444:Flunarizine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010424:Pentobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D010424:Pentobarbital; D009543:Nifedipine; D005444:Flunarizine