C-type natriuretic peptide-mediated coronary vasodilation: Role of the coronary nitric oxide and particulate guanylate cyclase systems

R. Scott Wright, Chi ming Wei, Cheol H. Kim, Masahiko Kinoshita, Yuzuru Matsuda, Lawrence L. Aarhus, John C. Burnett, Wayne L. Miller

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Objectives. We tested the hypothesis that C-type natriuretic peptide (CNP) mediates coronary vasodilation through activation of cyclic guanosine monophosphate (cGMP) by way of particulate guanylate cyclase. Background. CNP has known peripheral vasodilator properties, and preliminary 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 vasodilation, and immunohistochemical staining was utilized to localize the presence of CNP in the coronary endothelium. Results. CNP relaxed isolated coronary arteries with (mean ± SEM 45.9 ± 7%) and without (72.0 ± 7%) an endothelium (p < 0.05 for CNP effect alone, p < 0.05 for endothelium vs. no endothelium with CNP). Intracoronary infusions 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 ± 0.3). Intracoronary injections increased coronary blood flow (Δ baseline coronary flow, 30 ± 9 ml/min [p < 0.05]). HS-142-1 significantly attenuated these increases (Δ coronary flow, 30 ± 9 ml/min [CNP] to 14 ± 6 [CNP + HS-142-1] [p < 0.05 CNP vs. CNP + HS-142-1]) and the relaxation of organ chamber rings (56 ± 7% [CNP] to 18 ± 6% [HS-142-1 + CNP]). Finally, CNP was localized to the coronary endothelium and smooth muscle by immunohistochemical staining. Conclusions. CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary vasodilation is attenuated by intracoronary HS-142-1. Intracoronary HS-142-1 does not affect acetylcholine-mediated coronary vasodilation. These observations support a role for exogenous CNP as a potent coronary vasodilator.

Original languageEnglish (US)
Pages (from-to)1031-1038
Number of pages8
JournalJournal of the American College of Cardiology
Volume28
Issue number4
DOIs
StatePublished - Oct 1996

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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