Cocaine activates the renin-angiotensin system in pregnant rabbits and alters the response to ischemia.
The purpose of this study was to determine (1) if the acute in vivo administration of cocaine and the cocaine metabolite ecgonine methyl ester (EME) activates the renin-angiotensin system (RAS) and alters cardiovascular function during pregnancy and (2) whether heart function is decreased in rabbits chronically exposed to cocaine or EME in vivo. The acute in vivo effects on plasma renin activity (PRA) were examined when cocaine (2 mg/kg) or EME (2 mg/kg) was administered intravenously. Arterial blood samples were withdrawn for hormonal analysis. Arterial pressure was measured using a COBE CDX III transducer and a Micro-Med 100 blood pressure analyzer. Hematocrit was measured using a microcapillary technique and serum protein was analyzed using refractometry. In chronic cocaine and EME studies, cardiovascular function was monitored in rabbits that were chronically exposed to cocaine or EME via Alzet osmotic pumps (1.66 microg/h for 14 d) implanted subcutaneously. On d 14, the animal was euthanized, and the heart was removed and exposed to 15 min of global ischemia using the Langendorff method. Coronary flow and left ventricular pressure (LVP) were assessed. The acute administration of cocaine or EME increased PRA and mean arterial pressure (MAP) in pregnant rabbits within 5 min. Coronary flow and LVP were significantly lower in the cocaine and EME-treated rabbits than in vehicle female rabbits.
Hargrave
Barbara
B
Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA. bhargrav@odu.edu
Lattanzio
Frank
F
D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006400:Hematocrit; D007273:Injections, Intramuscular; D008297:Male; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000503:physiopathology; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D011247:Pregnancy / Q000187:drug effects*; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced* / Q000503:physiopathology; D011817:Rabbits; D012083:Renin / Q000097:blood / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D017725:Ventricular Pressure / Q000187:drug effects
D000779:Anesthetics, Local; D001798:Blood Proteins; D014677:Pharmaceutical Vehicles; D014662:Vasoconstrictor Agents; D012083:Renin; D003042:Cocaine; C034524:ecgonine methyl ester