Cocaine increases circulating levels of atrial natriuretic peptide and pro atrial natriuretic peptide N-terminal fragment in conscious rats.
We examined the effects of intravenously administered cocaine (1 and 3 mg/kg) on haemodynamics (mean arterial pressure, heart rate and right atrial pressure), plasma immunoreactive atrial natriuretic peptide (immunoreactive ANP) and immunoreactive N-terminal peptide of proANP (immunoreactive N-terminal ANP) in conscious, chronically cannulated Sprague-Dawley rats. The direct effect of cocaine (10(-6)-10(-4) M) was also studied in primary cultures of neonatal rat cardiac ventricular myocytes. Intravenous injection of 1 mg/kg or 3 mg/kg of cocaine caused an immediate peak rise in mean arterial pressure (1 mg/kg: 44 +/- 3 mm Hg, n = 8; 3 mg/kg 49 +/- 2 mm Hg, n = 12), which was followed by a dose-dependent sustained pressor response. The right atrial pressure rose simultaneously and 10-20 s later heart rate decreased. Plasma immunoreactive ANP levels increased significantly (1 mg/kg: 56 +/- 10 pmol/1; n=8; 3 mg/kg: 130 +/- 54; n = 12) and also immunoreactive N-terminal ANP levels rose significantly 2 min after the injection of the higher cocaine dose (230 +/- 27 pmol/l, n = 12). Significant correlations between plasma immunoreactive ANP levels and all haemodynamic variables were found, especially between mean arterial pressure and plasma immunoreactive ANP levels (r = 0.86, P < 0.001). In neonatal rat ventricular myocyte cultures, the highest concentration of cocaine (10(-4) M) reduced ANP release into the incubation medium (-41 +/- 14%, n = 5) but the reduction was not statistically significant. Our results show that cocaine dose dependently increases ANP and N-terminal ANP secretion into the circulation in conscious rats and that this increase is mediated by haemodynamic changes. Thus, plasma ANP and N-terminal ANP levels could be used as markers for acute cocaine-induced cardiac toxicity.
Pelkonen
M
M
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Luodonpää
M
M
Vuolteenaho
O
O
Pasanen
M
M
Ruskoaho
H
H
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
C099254:N-terminal proatrial natriuretic peptide; D011498:Protein Precursors; D014662:Vasoconstrictor Agents; D009320:Atrial Natriuretic Factor; D003042:Cocaine