NORCOCAINE IS A POTENT MODULATOR OF HEMODYNAMIC-RESPONSES, PLASMA-CATECHOLAMINES AND CARDIAC HORMONE-RELEASE IN CONSCIOUS RATS

We examined the effects of intravenously administered cocaine and norc ocaine on the haemodynamics, the plasma immunoreactive atrial natriure tic peptide (ANP), the N-terminal peptide of proANP (NT-ANP) and the p lasma catecholamine levels in conscious, chronically cannulated Spragu e-Dawley rats. Cocaine caused an immediate significant peak rise in th e mean arterial pressure which was followed by a dose-dependent sustai ned presser response. Cocaine also decreased the heart rate and increa sed the right atrial pressure. Norcocaine at a dose of 1 mg/kg maximal ly decreased the heart rate which did not recover to the basal level w ithin 15 min. Norcocaine (1 mg/kg) did not affect the right atrial pre ssure but with a dose of 3 mg/kg an elevation of 2.2 +/- 0.3 mmHg (P < 0.005) was observed which did not recover to the control level during the 30 min study period. Plasma immunoreactive ANP and NT-ANP levels increased significantly in a dose-dependent manner after the injection of cocaine. Norcocaine treatments also resulted in significant correl ations between ANP or NT-ANP levels and haemodynamic variables, especi ally between the right atrial pressure and the plasma immunoreactive A NP levels (r = 0.58, n = 28, P < 0.005). Cocaine and norcocaine enhanc ed the plasma adrenaline levels but norcocaine, already at a dose of 1 mg/kg, caused a maximal increase in the plasma adrenaline levels. The long lasting increase in the right atrial pressure after norcocaine a nd the decrease in the heart rate after higher doses of cocaine sugges t the role for this metabolite, or a further metabolite of norcocaine, in the cardiovascular and haemodynamic responses to cocaine seen in c onscious rats. (C) 1998 Elsevier Science Ireland Ltd. All rights reser ved.