Propranolol promotes cocaine-induced spasm of porcine coronary artery.
Case reports suggest that cocaine use is associated with acute myocardial infarction which may be due to coronary spasm. The present study reports the effect of cocaine on the isolated coronary artery. Ring segments were prepared from the porcine left anterior descending coronary artery and suspended in tissue baths under isometric conditions. Cocaine was ineffective by itself in promoting contraction, but a cumulative concentration-response curve was obtained in the presence of DL-propranolol (1.3 x 10(-6) M); D-propranolol failed to promote cocaine-induced vasoconstriction. The maximum contractile response to cocaine was one-third of the response to histamine and was in the same range as the response to U46619, prostaglandin F2 alpha and norepinephrine. Phenylephrine had a weak effect. In the presence of DL-propranolol, the vasoconstrictive effect of cocaine was subject to rapid tachyphylaxis. Prazosin (5 x 10(-9) M), also in the presence of DL-propranolol, significantly displaced the cocaine concentration-response curve to the right and diminished contractile force by one-half. We conclude that cocaine-induced coronary vasoconstriction elicited in the presence of DL-propranolol can be mediated through local adrenergic mechanisms involving beta receptor antagonism and activation of both alpha-1 and alpha-2 adrenoceptors.
Vargas
R
R
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia.
Gillis
R A
RA
Ramwell
P W
PW
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004357:Drug Synergism; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D013237:Stereoisomerism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D011433:Propranolol; D003042:Cocaine; D009638:Norepinephrine; D011224:Prazosin