Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats.
1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D004347:Drug Interactions; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D010869:Pindolol / Q000008:administration & dosage / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride; D013564:Sympathetic Nervous System / Q000502:physiology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D008464:Mecamylamine; D011433:Propranolol; D011335:Proadifen; D010869:Pindolol