Section 9
Chapter 8,339

Cocaine increases circulating levels of atrial natriuretic peptide and pro atrial natriuretic peptide N-terminal fragment in conscious rats

Pelkonen, M.; Luodonpää, M.; Vuolteenaho, O.; Pasanen, M.; Ruskoaho, H.

European Journal of Pharmacology 304(1-3): 55-62


ISSN/ISBN: 0014-2999
PMID: 8813584
DOI: 10.1016/0014-2999(96)00108-2
Accession: 008338675

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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.