Effects of urapidil on coronary blood flow during graded treadmill exercise

We examined the effects of the alpha-adrenergic blocking agent urapidil on coronary blood flow (CBF) and myocardial O2 consumption during exercise in 11 dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery (LCX) BF was measured with an electromagnetic flowmeter, and aortic and coronary sinus electromagnetic flowmeter, and aortic and coronary sinus catheters allowed determination of myocardial arteriovenous O2 extraction. During control conditions, graded treadmill exercise caused progressive increases in myocardial O2 consumption, which resulted from regular increases in CBF as well as increased O2 extraction by myocardium. Urapidil 3 mg/kg blocked the response to the selective alpha 1-adrenergic agonist phenylephrine (PE 5 micrograms/kg intravenously, i.v.), and significantly decreased arterial blood pressure (BP) at rest and during exercise. Heart rate (HR) was significantly faster than control during the lightest level of exercise after urapidil. Similarly, CBF was significantly increased during light and moderate exercise after urapidil administration. Urapidil caused a slight decrease in myocardial O2 extraction, with an increase in coronary sinus O2 tension. These data indicate that urapidil antagonized adrenergic coronary vasoconstriction, which acted to limit the increase in CBF that occurred during exercise.