C-TYPE NATRIURETIC PEPTIDE-MEDIATED CORONARY VASODILATION - ROLE OF THE CORONARY NITRIC-OXIDE AND PARTICULATE GUANYLATE-CYCLASE SYSTEMS

Objectives. We tested the hypothesis that C-type natriuretic peptide ( CNP) mediates coronary vasodilation through activation of cyclic guano sine monophosphate (cGMP) by way of particulate guanylate cyclase. Bac kground. CNP has known peripheral vasodilator properties, and prelimin ary data have suggested that it can function as a coronary vasodilator . Methods. The actions of CNP were studied in instrumented dogs and in organ chamber rings in the presence and absence of a known antagonist to particulate guanylate cyclase, HS-142-1. Additionally, the actions of HS-142-1 were tested on acetylcholine-mediated coronary vasodilati on, and immunohistochemical staining was utilized to localize the pres ence of CNP in the coronary endothelium. Results. CNP relaxed isolated coronary arteries with (mean +/- SEM 45.9 +/- 7%) and without (72.0 +/- 7%dagger) an endothelium (*p < 0.05 for CNP effect alone, dagger p < 0.05 for endothelium vs. no endothelium with CNP). Intracoronary i nfusions increased coronary blood flow (baseline, 64.6 +/- 5.1 ml/min; CNP-5, 79.9 +/- 6.1; CNP-20, 103.3 +/- 13.6* [*p < 0.05 vs. baseline value]) and reduced coronary vascular resistance (baseline, 1.6 +/- 0 .3 mm Hg/ml per min; CNP-5, 1.4 +/- 0.3; CNP-20, 1.2 a 0.3*). Intraco ronary injections increased coronary blood flow (Delta baseline corona ry flow, 30 +/- 9 ml/min [*p < 0.05]). HS-142-1 significantly attenua ted these increases (Delta coronary flow, 30 +/- 9 ml/min [CNP] to 14 +/- 6 dagger [CNP + HS-142-1] [dagger p < 0.05 CNP vs. CNP + HS-142-1 ]) and the relaxation of organ chamber rings (56 +/- 7% [CNP] to 18 +/ - 6%dagger [HS-142-1 + CNP]). Finally, CNP was localized to the corona ry endothelium and smooth muscle by immunohistochemical staining. Conc lusions. CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary v asodilation is attenuated by intracoronary HS-142-1. Intracoronary HS- 142-1 does not affect acetylcholine-mediated coronary vasodilation. Th ese observations support a role for exogenous CNP as a potent coronary vasodilator.