Positive chronotropic responses produced by alpha-adrenoreceptors in the pithed rat.
1 Phenylephrine (1-100 microgram/kg, intravenously) produced dose-dependent increases in heart rate and blood pressure in the pithed rat. 2 The positive chronotropic response to phenylephrine (10 microgram/kg) was reduced in a dose-dependent manner by propranolol (0.01-0.3 mg/kg), but higher doses of propranolol (up to 3 mg/kg) did not reduce the response by more than about 50%. The residual response was virtually abolished by phentolamine (0.3 mg/kg) or prazosin (3 microgram/kg). Labetalol (3 mg/kg) which has both alpha- and beta-blocking activity, also abolished the positive chronotropic response. 3 The pressor response to phenylephrine (1-30 microgram/kg) was enhanced by propranolol (1 mg/kg) and abolished by phentolamine (1 mg/kg) and prazosin (30 microgram/kg). Labetalol (3 mg/kg) reduced the response to phenylephrine by 73%. 4 Propranolol (0.3 mg/kg) completely blocked the chronotropic and vasodepressor effects of isoprenaline (0.1 microgram/kg). 5 It is concluded that phenylephrine acts on both alpha 1- and beta 1-adrenoreceptors to produce an increase in heart rate, on alpha 1-adrenoreceptors to produce vasoconstriction and on beta 2-adrenoreceptors to produce vasodilation. This latter effect is usually masked by the predominant vasoconstrictor action.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats / Q000502:physiology*; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000494:pharmacology*; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011433:Propranolol