POSITIVE CHRONOTROPIC RESPONSES PRODUCED BY α-ADRENORECEPTORS IN THE PITHED RAT

• 1 Phenylephrine (1–100 γg/kg, intravenously) produced dose-dependent increases in heart rate and blood pressure in the pithed rat.
• 2 The positive chronotropic response to phenylephrine (10 μg/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 μg/kg). Labetalol (3 mg/kg) which has both α- and β-blocking activity, also abolished the positive chronotropic response.
• 3 The pressor response to phenylephrine (1–30 μg/kg) was enhanced by propranolol (1 mg/kg) and abolished by phentolamine (1 mg/kg) and prazosin (30 μg/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 μg/kg).
• 5 It is concluded that phenylephrine acts on both α₁- and β₁-adrenoreceptors to produce an increase in heart rate, on α₁-adrenoreceptors to produce vasoconstriction and on β₂-adrenoreceptors to produce vasodilation. This latter effect is usually masked by the predominant vasoconstrictor action.