The haemodynamic profile of cromakalim in the cat.
The haemodynamic profile of the novel antihypertensive agent, cromakalim (BRL 34915), has been studied in conscious and anaesthetised cats. Given orally (0.03 and 0.06 mg/kg) to conscious cats and by intravenous infusion (0.002 mg/kg/min for 7-10 min) to anaesthetised animals, cromakalim reduced arterial pressure (AP; systolic/diastolic) and total peripheral resistance (TPR) while increasing cardiac output (CO) via both its components [heart rate (HR) and stroke volume (SV)]. In both models, HR changes were minimal for reductions of AP approaching 20 mm Hg. In a second group of conscious cats, cromakalim increased mean renal blood flow (MRBF) at hypotensive doses (0.03 and 0.06 mg/kg orally); HR was only significantly raised following the higher dose of cromakalim. In anaesthetised animals, intravenously infused cromakalim had little effect on central venous pressure and increased cardiac contractility. The data indicate that cromakalim lowers AP by reducing TPR with minimal increase in HR. In addition, cromakalim has a potentially beneficial effect on MRBF.
Clapham
J C
JC
Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, U.K.
Buckingham
R E
RE
D000758:Anesthesia; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D019806:Cromakalim; D004567:Electrodes, Implanted; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D001578:Benzopyrans; D011758:Pyrroles; D019806:Cromakalim