Cocaine-induced suppression of renin secretion is mediated in the brain: investigation of cardiovascular and local anesthetic mechanisms.
Acute cocaine reduces renin secretion. To determine a peripheral versus central site of action, intracerebroventricular (ICV) versus intraperitoneal (IP) injections of cocaine were compared. Cocaine was more potent reducing plasma renin activity (PRA) and concentration (PRC) when injected ICV (0.050 mg/kg) than IP (5 mg/kg), suggesting a central site of action. Furthermore, addition of cocaine (10(-4) M) to kidney slices in vitro did not influence renin release, indicating that cocaine does not suppress renin secretion by acting directly in the kidney. We also investigated whether the hypertensive or local anesthetic properties of cocaine mediate its inhibition of renin secretion. Therefore, we compared the cardiovascular and endocrine effects of cocaine with those of the local anesthetic drug procaine. Both cocaine and procaine (500 micrograms/kg, ICV) produced rapid and short-term increases in blood pressure, but cocaine decreased PRC whereas procaine increased PRC. Intra-arterial (IA) and IP injections of cocaine also reduced PRC whereas procaine had no effect (IA) or elevated PRC (IP). Together, the data suggest that cocaine decreases renin secretion by acting in the brain. It is not likely that the cardiovascular or local anesthetic actions of cocaine are the main cause of its suppressive effect on renin secretion.
Van de Kar
L D
LD
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153.
Levy
A D
AD
Rittenhouse
P A
PA
Li
Q
Q
Alvarez Sanz
M C
MC
Yracheta
J
J
Kunimoto
K
K
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003864:Depression, Chemical; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011343:Procaine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*
D000779:Anesthetics, Local; D011343:Procaine; D012083:Renin; D003042:Cocaine; D007545:Isoproterenol