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STUDIES ON THE CARDIOVASCULAR EFFECTS OF PINDOLOL IN DOCA/SALINE HYPERTENSIVE RATS
Author(s) -
BUCKINGHAMM R.E.,
HAMILTON C.,
ROBSON D.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb07523.x
Subject(s) - pindolol , medicine , propranolol , heart rate , blood pressure , endocrinology , tachycardia , isoprenaline , saline , stimulation , pharmacology , anesthesia
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 μg/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 μg/kg) in DS‐rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by β‐adrenoceptor stimulation. 3 After mecamylamine (10 mg/kg), oral pindolol (50 μg/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 μg/kg) resulted in a reduction of neuronally‐induced tachycardia in pithed DS‐rats; neuronally‐evoked pressor effects were also antagonized by pindolol (50 μg/kg, orally). 5 Whereas pindolol, 50 μg/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 β‐adrenoceptor blockade was produced by pretreatment with pindolol, 50 μg/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 μg/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 μg/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 β‐adrenoceptors.