Renal sympathetic and systemic vascular responses to cocaine are correlated in conscious rats

Abstract

Cocaine elicits hemodynamic responses that are dependent on activation of central sympathoexcitatory pathways. We reported that greater vascular responses to cocaine are associated with greater increases in sympathetic nerve activity (SNA). We also reported that i.v. or intracerebroventricular propranolol enhances the cocaine induced increase in systemic vascular resistance (SVR). We hypothesized that this increase in SVR was due to a greater increase in SNA. Male Sprague Dawley rats were instrumented for measurement of cardiac output, heart rate, arterial pressure and renal SNA. After a minimum of 3 days for recovery, conscious animals were subjected to cocaine. Ganglionic blockade (trimethaphan, 10 mg/kg i.v.) was used to determine background activity. Cocaine (5 mg/kg i.v.) increased arterial pressure, SVR and renal SNA. Rats, pretreated with propranolol (1 mg/kg i.v.) 10 min. before administration of cocaine, had a greater cocaine‐induced increase in SVR that was associated with a greater increase in renal SNA. Therefore, there was a positive correlation between SVR and renal SNA. We conclude that propranolol increases SVR likely due to an increased central sympathoexcitation. Supported by USPHS NIH R01 DA0017371, DA05180 and training grant 5T32 GM008306.