ADENYLATE-CYCLASE ACTIVATION PROMOTES THE RECRUITMENT OF CORONARY VASODILATOR RESERVE AND IMPROVES SUBENDOCARDIAL CONTRACTILITY DURING CORONARY HYPOPERFUSION

This study was designed to examine the effects of an adenylate cyclase activator, NKH477, on epicardial and endocardial contraction and coro nary blood flow (CoF) in the presence or absence of ischemia and to co mpare it to those of adenosine. We measured coronary pressures (CoP), coronary blood flow, epicardial and endocardial wall thickening (i.e., %EPWT and %ENWT, respectively, by sonomicrometry) in 18 anesthetized dogs. The left circumflex coronary artery was perfused with arterial b lood using a pressure controlled servo pump. Propranolol (0.5 mg/kg) a nd atropine (0.25 mg) were used to minimize the neurogenic effects. Co P decreased from 100 mm Hg to 40 mm Hg with and without drugs. At CoP of 100 mm Hg, intracoronary infusion of NKH477 (10(-8) M/kg/min) produ ced a two-fold increase in CoF, but there were no changes in either th e %EPWT or the %ENWT. During coronary hy pofusion at coronary pressure s equal to 40 mm Hg, NKH477 increased CoF from 16 +/- 2 to 28 +/- 4 mL / min (p < 0.05) and improved %ENWT significantly from 6 +/- 7 to 23 /- 7% (p < 0.05). However %EPWT was not improved by NKH477. On the oth er hand, the intracoronary infusion of adenosine (10 mu g/kg/min) incr eased CoF from 16 +/- 5 to 21 +/- 6 mL/min (p < 0.05) at CoP of 40 mm Hg. However, this dose of adenosine failed to improve %ENWT (16 +/- 10 % vs. 14 +/- 10%, n.s.). Thus, the improvement of subendocardial funct ion by NKH477 might be related to the improvement of subendocardial pe rfusion which could be induced by the potentiation of endogenously rel eased adenosine as well as the direct vasodilator effect. This contras ts with the effects of exogenously administered adenosine, which faile d to improve subendocardial contractility.