Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease.
Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Kern
M J
MJ
Horowitz
J D
JD
Ganz
P
P
Gaspar
J
J
Colucci
W S
WS
Lorell
B H
BH
Barry
W H
WH
Mudge
G H
GH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010879:Piperazines / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D014665:Vasodilator Agents; C005185:trimazosin; D009638:Norepinephrine