Alpha 2-adrenergic coronary constriction in ischemic myocardium during exercise.
The effect of either selective alpha 1- or alpha 2-adrenoceptor blockade on ischemic myocardial blood flow and function was examined in beta-blocked dogs trained to run on a motor-driven treadmill. The animals were instrumented with sonomicrometers for the assessment of regional systolic wall thickening (%WTh) of the left ventricle. For drug infusion, an intracoronary catheter was implanted in the circumflex coronary artery and a hydraulic cuff was placed proximally around the artery. Following systemic beta-blockade with 0.8 mg/kg propranolol, an acute stenosis of the circumflex coronary artery inflated during exercise induced severe dysfunction in the posterior wall. Intracoronary infusion of 80 micrograms/kg of the selective alpha 2-adrenoceptor blocking agent idazoxan improved posterior wall (PW)-%WTh from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.06) and regional myocardial blood flow (radiolabelled microspheres) in the subendocardium of the posterior wall from 0.17 +/- 0.05 to 0.45 +/- 0.30 (ml/min)/g (p less than 0.05). No increases in regional blood flow and regional myocardial function were observed after infusion of the selective alpha 1-adrenoceptor blocking agent prazosin (20 micrograms/kg) under the same experimental conditions. It is concluded that during severe ischemia, significant postjunctional alpha 2-adrenoceptor mediated coronary vasoconstriction exists. Regional alpha 2-adrenoceptor blockade, but not alpha 1-adrenoceptor blockade is effective in reducing regional ischemia and dysfunction by attenuating sympathetic vasoconstriction in the conscious dog.
Seitelberger
R
R
Seaweed Canyon Laboratory, Department of Medicine, University of California, San Diego, School of Medicine.
Guth
B D
BD
Heusch
G
G
Ross
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D019329:Idazoxan; D005082:Physical Exertion / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D011224:Prazosin; D019329:Idazoxan