THE ROLE OF THE AUTONOMIC NERVOUS SYSTEM IN THE RESPONSES OF THE PERFUSED CANINE PAW TO PROSTAGLANDINS B₁ AND B₂

¹ Departments of Internal Medicine and Pharmacology, College of Medicine, University Hospitals, Iowa City, Iowa

The interaction between the autonomic nervous system and prostaglandin B₂ (PGB₂) and prostaglandin B₁ (PGB₁)-induced vasoconstriction was evaluated in the normally innervated and acutely denervated canine hindpaw perfused with autologous blood at constant flow. Intra-arterial infusions of PGB₂ (50-1600 ng/kg/min) produced concentration-dependent vasoconstriction. Pretreatment of dogs with bretylium (20 mg/kg i.v.), phentolamine (2 mg/kg i.v.), reserpine (0.5 mg/kg/day for 2 days) or acute denervation unmasked a vasodilator component to PGB₂ and reduced the magnitude of the constrictor response to this prostaglandin. However, the constrictor response to PGB₂ could not be abolished by adrenergic blocking agents. In contrast to these findings, low concentrations of PGB₁ (50-200 ng/kg/min) dilated the canine hindpaw whereas higher concentrations (200-3200 ng/kg/min) resulted in cutaneous vasoconstriction. PGB1 is 8 times less potent a vasoconstrictor than PGB₂. Bretylium and phentolamine, reserpine and acute denervation also reduced the vasoconstrictor response to PGB₁. These findings suggest that 1) PGB₂ and PGB₁ act directly on smooth muscle to cause both vasodilation and vasoconstriction, 2) a portion of the vasoconstrictor respouse to these prostaglandins is mediated by PGB-induced release of catecholamines from adrenergic nerve terminals and 3) PGB-induced release of catecholamines appears to be dependent on the electrical impulse activity along the sympathetic adrenergic fibers.