Nonadrenergic mechanisms of cocaine-induced regional vascular responses in rats.
The pressor response to cocaine is a consequence of mesenteric vasoconstriction and hindquarters vasodilation as a result of activation of alpha 1- and beta-adrenergic receptors, respectively. In the present study, evidence for additional, nonadrenergic effects of cocaine-induced changes in regional blood flow was obtained using pulsed Doppler flowmetry in conscious rats. Cocaine produced dose-dependent initial peaks (within 1 min) in mean arterial pressure concomitant with an increase in hindquarters and mesenteric vascular resistance. The sustained, modest pressor response was associated with hindquarters vasodilation and bradycardia. The cocaine-induced vasodilation was enhanced by pretreatment with indomethacin (5 mg/kg), prevented by ibuprofen (12.5 mg/kg) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C, 10.5 mg/kg) pretreatment, and unaffected by meclofenamate administration (2.5 mg/kg). Equipotent local anesthetic doses of procaine produced equivalent hindquarters vasodilator responses and more modest pressor responses. Dial-urethane anesthesia did not affect hindquarters vasodilation in response to cocaine or procaine but did reduce the mesenteric vasoconstrictor and pressor responses. These data demonstrate that the cocaine-induced hindquarters vasodilation is not mediated solely by beta-adrenergic receptors but is also dependent upon eicosanoids. Furthermore, the cocaine-induced vasodilation may be due, in part, to a direct local anesthetic effect but is not dependent upon a locomotor or behavioral stress induced increase in blood flow.
Knuepfer
M M
MM
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, MO 63104.
Branch
C A
CA
Wehner
D M
DM
Gan
Q
Q
Hoang
D
D
D000768:Anesthesia, General; D000772:Anesthesia, Local; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology*; D011343:Procaine / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011343:Procaine; D003042:Cocaine; D009638:Norepinephrine