Anaesthetised normotensive rats for the detection of hypotensive activity of a beta-adrenoceptor antagonist and other antihypertensive agents.
A simple method for the detection of antihypertensive activity in anaesthetised (66 mg/kg i. v. alpha-chloralose and 20 mg/kg i. v. aprobarbital) normotensive rats is described. Dihydralazine (0.5 to 2 mg/kg i. v.) reduced blood pressure dose-dependently but did not provoke the anticipated tachycardia. Clonidine (1 to 8 microgram/kg i.a.), guanethidine (0.5 to 5 mg/kg i.a.) and alpha-methyldopa (2.5 to 10 mg/kg i.a.) reduced blood pressure dose-dependently; the effect of reserpine (0.1 to 1.0 mg/kg i.a) was, however, not dose-dependent. Although all four drugs reduced heart rate, only clonidine and guanethidine did so in a dose-dependent manner. Phentolamine (0.5 to 2 mg/kg i. v.) and propranolol (0.01 to 1 mg/kg i. v.) elicited dose-dependent falls in blood pressure. Whereas phentolamine increased heart-rate slightly, propranolol elicited a bradycardia. It is concluded that the chloralose-aprobarbital anaesthetised rat is a suitable and economical model for the screening of potential antihypertensive agents including beta-adrenoceptor antagonists. However, reflex trachycardia provoked by peripheral vasodilators may not be apparent.
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents; D001463:Barbiturates / Q000494:pharmacology; D002698:Chloralose / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004078:Dihydralazine / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001463:Barbiturates; D002698:Chloralose; D008750:Methyldopa; D012110:Reserpine; D011433:Propranolol; D003000:Clonidine; D004078:Dihydralazine; D010646:Phentolamine; D006145:Guanethidine