Inhibition of the carotid sinus reflex by the chronic administration of propranolol

Abstract

PIlar,uac'uh'ic'. Di)ivisioii, Imipcrial Chlemiical Inidustrie.s Limitedl, A lderlev Park, MaCcle,.fiw/1dl1. The changes in heart rate and arterial pressure produced by the intravenous injection of isoprenaline (05 [rg/kg), noradrenaline (10 jg/kg), phenylethylamine (0.5 mg/kg), amphetamine (0 5 mg/kg) and by bilateral occlusion of the carotid arteries and by stimulation of the central ends of both vagus nerves have been recorded in groups of dogs anaesthetized with pentobarbitone.2. The acute intravenous injection of propranolol (1 mg/kg) reduced the increases in heart rate produced by the six procedures, the increases in arterial pressure in response to the last five procedures and the decrease in pressure produced by isoprenaline. 3. This decrease produced by propranolol in the pressor responses resulted from a reduction in the increases in cardiac output elicited by the five procedures and has been attributed to blockade of cardiac adrenergic ,0-receptors. 4. Three groups of dogs were pretreated for 6 weeks by the oral administration of either placebo, propranolol 50 mg/kg daily or propranolol 10 mg/kg twice daily. The responses to the six test procedures were obtained 17 24 hr after the last dose of propranolol, when only minimal blockade of adrenergic /99-receptors was present. In the propranolol-treated groups, the pressor response to carotid occlusion but not to the other test procedures was significantly reduced. 5. The pressor response to carotid occlusion was not reduced in a fourth group ot dogs given a single dose of propranolol (50 mg/kg) 24 hr before the test procedures. 6. The mechanism of this selective reduction in the pressor response to occlusion of the carotid arteries is not clear. It is suggested that it may contribute to the hypotensive action of propranolol in man during prolonged oral administration.Several reports have shown that the intravenous injection of propranolol (5 15 mg) under resting conditions in patients with normal or raised arterial pressure

Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents.

“…99 Experiments in dogs have shown that chronic propranolol therapy reduces the pressor responses to carotid occlusion, while short-term therapy is without effect. 108 These results could be related to an increased baroreceptor sensitivity or due to central nervous system effects of /S-adrenoceptor blocking agents.…”

“…108 Yet, after intravenous administration of propranolol, there is a rapid fall in plasma renin levels but no decrease in BP, 105> m In addition, several clinical studies failed to show a correlation between the BP fall induced by /S-adrenoceptor antagonists and renin levels in plasma. 99 Experiments in dogs have shown that chronic propranolol therapy reduces the pressor responses to carotid occlusion, while short-term therapy is without effect.…”

Absence of Changes in Drug Disposition and Catecholamine Sensitivity in the Hyperthyroid Dog

“…For P-blockade assessment, both the absolute reduction (R) in beats/min of isoprenaline-induced tachycardia (Kaplan & Commarato, 1973) and the percentage reduction (%R) from the control (Black, Duncan & Shanks, 1965;Dunlop & Shanks, 1969) were calculated at the same time schedule as the chronotropic response after the drug injection. The absolute reduction (R) is the difference between the isoprenaline-induced increase of the heart rate before and after the drug.…”

Effect of propranolol on noradrenaline kinetics in patients with essential hypertension.

“…Early reports of inhibition of sympathetic nervous system cardiovascular reflexes during f3-adrenergic blockade, both in animals (Dunlop & Shanks, 1969) and patients with essential hypertension (Esler & Nestel, 1973), suggested that suppression of the sympathetic nervous system, perhaps at a site within the central nervous system (Kelliher & Buckley, 1970), might be an antihypertensive mechanism. This viewpoint was subsequently strengthened when it was found that administration of propranolol to rabbits reduced sympathetic nerve firing rates (Lewis & Haeusler, 1975).…”