Effects of pinacidil on arterial and venous resistances and mean circulatory filling pressure in rats.
1. The effects of the potassium channel opener, pinacidil, on mean arterial pressure (MAP), mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In pentobarbitone-anaesthetized rats given mecamylamine (ganglionic blocker, 3.7 micrograms kg-1) and noradrenaline (1.5 micrograms kg-1 min-1) to suppress autonomic reflexes, pinacidil (60 and 180 micrograms kg-1 min-1), relative to the vehicle, reduced MAP and TPR in a dose-dependent manner but did not significantly alter CO, MCFP or RV. 3. Pinacidil (10-300 micrograms kg-1 min-1) caused similar increases in MCFP, an inverse index of venous compliance, and similar dose-dependent reductions in mean arterial pressure (MAP) in conscious, intact rats and rats infused with the ganglionic blocker, hexamethonium (150 micrograms kg-1 min-1). In rats with vasomotor tone elevated by the infusion of noradrenaline (1.5 micrograms kg-1 min-1), pinacidil caused markedly greater depressor responses but did not significantly alter MCFP. 4. Our results show that pinacidil is an efficacious vasodilator of arterial resistance blood vessels but has little venodilator activity.
Waite
R P
RP
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Lim
S L
SL
Pang
C C
CC
D000758:Anesthesia; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008863:Microspheres; D020110:Pinacidil; D051381:Rats; D017207:Rats, Sprague-Dawley; D018924:Vascular Capacitance / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
D005730:Ganglionic Blockers; D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil