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.