Effect on Pressor and Vascular Responsiveness in Rabbits of Drugs That Decrease Norepinephrine Uptake

The purpose of this study was to determine if decreases in norepinephrine (NE) uptake would result in pressor and vascular hyperresponsiveness to vasoconstrictor substances. These experiments examined the effects of cocaine and imipramine, drugs known to decrease NE uptake, on the changes in arterial pressure and total peripheral resistance (TPR) in response to NE and arginine vasopressin (AVP) in conscious rabbits. The infusion of graded doses of NE resulted in significantly greater increases in mean arterial pressure at all dose levels following the administration of cocaine (0.6 mg/kg iv) or imipramine (0.5 mg/kg) than following the administration of the vehicle alone. The infusion of NE also resulted in greater increases in TPR as well as blood pressure following cocaine or imipramine administration than occurred prior to the administration of these drugs. The infusion of AVP caused significantly larger increases in arterial pressure and in TPR following cocaine or imipramine administration than was seen after the administration of AVP to control rabbits not treated with these drugs. These studies demonstrated that cocaine and imipramine, substances known to decrease NE uptake by the sympathetic nerve terminals, will induce pressor and vascular hyperresponsiveness to NE and AVP in rabbits. These results are in keeping with the concept that pressor and vascular hyperresponsiveness in renal prehypertensive rabbits may be the result of decreases in NE uptake by sympathetic fibers supplying vascular smooth muscle cells.