Further Observations on the Pressor Action of Propranolol

Abstract

Propranolol was introduced by Black, Crowther, Shanks, Smith & Dornhorst (1964) as a potent 8-adrenergic receptor blocking agent. In the previous paper (Kayaalp & Kiran, 1966), evidence was presented for the fact that the sustained pressor response elicited by this drug in the sympathetically denervated perfused hind limbs of the dog is due to the release of catecholamines from the adrenal medulla.The present work was undertaken to determine if the release of catecholamines from the adrenal medulla is the only mechanism by which propranolol produces a vasoconstrictor response or it causes an increase in the sympathetic nervous activity on the vasculature of the perfused area in addition. An attempt has also been made to elucidate further the mechanism of the sustained pressor response to propranolol, particularly as observed after the blockade of the a-adrenergic receptors. METHODSDogs of either sex, weighing between 12 and 26 kg were used. They were anaesthetized by intravenous injection of sodium pentobarbital (30 mg/kg). The trachea was cannulated for free airway, and the left jugular vein was cannulated for intravenous injection of drugs. The procedures for surgery, perfusion and recording the systemic blood pressure and perfusion pressure were the same as previously described (Kayaalp & Kiran, 1966), except that both hind quarters were autoperfused together as described by Beck (1961).The sympathetic nerves to the perfused area were kept intact, and this was verified by the occurrence in the perfused area of a reflex vasodilatation in response to the rise in systemic blood pressure elicited by noradrenaline (0.3-0.5 ,Ag/kg, intravenously) or of a pressor response to bilateral occlusion of the common carotid arteries for 50 sec. Adrenal gland exclusionIn all dogs, except those with spinal cord section or nephrectomy and some of those pretreated with dichloroisoprenaline, the adrenal glands were excluded from the circulation in order to rule out the vasoconstrictor response to propranolol related to the release of catecholamines from the adrenal medulla (Kayaalp & Kiran, 1966). The right adrenal gland was reached through an incision along the lower edge of the last rib; the left adrenal gland was reached through the incision in the left flank done for the cannulation of the lumbar aorta for perfusion. The vascular connexions of the glands with the surrounding tissue were tied. The glands were left in place. Two hours were allowed to elapse before starting the experiment.

Pressor Response to β₁ and β₂-Blockers in Conscious Rats Treated with Phentolamine

“…This observation is in accordance with that of Kayaalp and Turker [18], who have shown that in the hind limb of dogs subjected to the infusion of phentolamine, propranolol caused a sustained rise in perfusion pressure, and with that of Regoli [9], who has shown that hypertension as a result of the adminis tration of p-blockers may be potentiated in the presence of an a-blocker. We have also found that the pressor effect of a p-antagonist or rather, the antagonism of the hypotensive effect of phentolamine, showed dose-depen dency and it occurred with a pr or piselective as well as a nonselective p-blocker.…”

Adrenalectomy abolishes antagonism of α‐adrenoceptor‐mediated hypotension by a β‐blocker in conscious rats

“…A paradoxical pressor response to the administration of a fiadrenoceptor antagonist has been shown to occur in rats anaesthetized with urethane (Kayaalp & Turker, 1967;Dasgupta, 1968;Yamamoto & Sekiya, 1969;Regoli, 1970;Sugawara et al, 1980;Himori et al, 1984). The pressor response in the anaesthetized rat was enhanced in the presence of an a-adrenoceptor antagonist (Yamamoto & Sekiya, 1969;Regoli, 1970;Sugawara et al, 1980).…”

Effects of Beta-Adrenergic Receptor Blocking Agents on Blood Pressure in Conscious Hypertensive Rats

“…The depletion of catecholarines by reserpine has been reported to develop more ,lowly and to he less complete in the adrenal medulla than in the other tissues including the heart and blood vessels (28). The vasoconstric tion caused by propranolol in anesthetized dog hind limb has been reported to be due to catecholamines released from the adrenal medulla (29,30).…”