The site and the mechanism of phenoxy-benzamine potentiation of the pressor response to oxytocin and vasopressin: in vivo and isolated aortic strips studies.

In intact rats, alpha adrenergic receptor blocking agents, phenoxybenzamine (PBZ) and phentolamine potentiated the pressor response to oxytocin and vasopressin (VP). In the presence of PBZ or phentolamine blockade, the dose-response curves of oxytocin and VP were shifted to the left, resulting in an apparent doubling of the pressor potency of the neurohypophysial peptides. The beta adrenergic blocking agent, propranolol had no significant effect on the pressor response to oxytocin or VP. Combined PBZ and propranolol blockade did not alter the potentiating activity of PBZ. The PBZ-potentiating effect seems to be specific to the neurohypophysial peptides, since the pressor response to angiotensin was not potentiated by PBZ. The potentiating effect of PBZ on VP could be demonstrated in isolated rat aortic strips. This clearly indicated that the site of action of PBZ is directly on the vascular smooth muscle. However, in aortic strips, the effect of PBZ was seen only if norepinephrine (NE) was also added to the bathing medium. NE alone had no significant effect on the contractile response to VP. The requirement of both PBZ and NE for the potentiating effect suggests that an interaction between these two agents is involved in the PBZ potentiation of VP response. The possibility that NE and not PBZ is the direct agent causing the potentiation of VP response is discussed.