C-type natriuretic peptide relaxes human coronary artery bypass grafts preconstricted by endothelin-1

Abstract

Background: Endothelin is implicated in graft spasm after coronary artery bypass grafting. We assessed reversal by the endothelium-derived vasodilator C-type natriuretic peptide of prior contraction of radial artery and other vessels commonly used for coronary artery bypass surgery.

Methods: Segments of human radial artery, saphenous vein, and internal mammary artery were mounted in organ baths after removal from patients undergoing cardiac surgery (n = 34; 64 +/- 2 years). Effects of increasing concentrations of C-type natriuretic peptide (with or without aprotinin, 1,000 U/mL) on endothelin-induced contraction were compared with acetylcholine, sodium nitroprusside, and papaverine.

Results: C-type natriuretic peptide relaxed endothelin precontraction in all vessels (F = 17.8, 36.3, and 48.4, respectively; p < 0.001), with maximum relaxations of 44%, 54%, and 66% in saphenous vein, internal mammary artery, and radial artery, respectively. Aprotinin did not affect relaxation to C-type natriuretic peptide. Acetylcholine relaxed the saphenous vein weakly, with maximal relaxation of 9% at 10(-6) M. However, the radial artery and internal mammary artery relaxed strongly to acetylcholine. The highest concentration of papaverine completely relaxed all vessels, but responses were less sensitive than to sodium nitroprusside or acetylcholine.

Conclusions: C-type natriuretic peptide reverses endothelin-induced constriction in arterial and venous conduits used for coronary artery bypass, particularly the radial artery. Proteolytic breakdown of C-type natriuretic peptide by local vascular enzymes appears of little importance in vitro. This signals the therapeutic potential of using C-type natriuretic peptide as an antagonist of graft vasospasm after coronary artery bypass surgery.