Norcocaine is a potent modulator of haemodynamic responses, plasma catecholamines and cardiac hormone release in conscious rats.
We examined the effects of intravenously administered cocaine and norcocaine on the haemodynamics, the plasma immunoreactive atrial natriuretic peptide (ANP), the N-terminal peptide of proANP (NT-ANP) and the plasma catecholamine levels in conscious, chronically cannulated Sprague-Dawley rats. Cocaine caused an immediate significant peak rise in the mean arterial pressure which was followed by a dose-dependent sustained pressor response. Cocaine also decreased the heart rate and increased the right atrial pressure. Norcocaine at a dose of 1 mg/kg maximally decreased the heart rate which did not recover to the basal level within 15 min. Norcocaine (1 mg/kg) did not affect the right atrial pressure 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 correlations between ANP or NT-ANP levels and haemodynamic variables, especially between the right atrial pressure and the plasma immunoreactive ANP levels (r = 0.58, n = 28, P < 0.005). Cocaine and norcocaine enhanced 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 and the decrease in the heart rate after higher doses of cocaine suggest the role for this metabolite, or a further metabolite of norcocaine, in the cardiovascular and haemodynamic responses to cocaine seen in conscious rats.
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
J
J
Mahlakaarto
H
H
Ruskoaho
P
P
Huttunen
E
E
MacDonald
M
M
Pasanen
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011498:Protein Precursors / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines; D018765:Dopamine Uptake Inhibitors; D011498:Protein Precursors; C008671:norcocaine; D009320:Atrial Natriuretic Factor; D003042:Cocaine