An Antihypertensive Action of Propranolol in Doca/Salt-Treated Rats

SUMMARY 1. The cardiovascular effects of acute and long-term (4–7 weeks) treatment with propranolol and guanethidine were observed in conscious, DOCA/salt-treated hypertensive rats. 2. During long-term treatment with a low dose of propranolol (0.2 mg/kg, subcutaneously, twice daily), the blood pressure is reduced to normotensive levels. 3. The subcutaneous injection of 0.2 mg/kg of propranolol lowers blood pressure and heart rate for 2–4 h at the start of long-term treatment, but these acute effects become less as treatment continues. 4. Long-term treatment with a high dose of propranolol (5 mg/kg, subcutaneously, twice daily) reduces heart rate but not blood pressure. 5. The acute effects of subcutaneous injection of 5 mg/kg of propranolol are a rise in blood pressure and a fall in heart rate; these effects are maintained throughout the period of long-term treatment. 6. Guanethidine (5 mg/kg, subcutaneously, once daily) produces a gradual fall in blood pressure. The acute depressor effect becomes less as treatment continues. 7. Observations were made on the responses to noradrenaline injections and thoraco-lumbar stimulation in pithed rats, pretreated 1 h beforehand with propranolol (0.2 or 5 mg/kg) or guanethidine (5 mg/kg). 8. Pressor responses to noradrenaline are slightly increased by all three pretreatments; the tachycardia produced by noradrenaline is increased by guanethidine and reduced by propranolol. 9. The pressor response to thoraco-lumbar stimulation is abolished by guanethidine and not affected by either dose of propranolol; the tachycardia is reduced by guanethidine and the high dose of propranolol (5 mg/kg) but not by the low dose. 10. The antihypertensive action of propranolol in DOCA/salt-treated rats can not be attributed to adrenergic neurone blockade or to a non-specific depressant effect, and does not appear to be due to a dose-dependent antagonistic effect on cardiac β-receptors. It is suggested that it is due to a central impairment of sympathetic activity.