TY - JOUR
T1 - C-type natriuretic peptide-mediated coronary vasodilation
T2 - Role of the coronary nitric oxide and particulate guanylate cyclase systems
AU - Wright, R. Scott
AU - Wei, Chi ming
AU - Kim, Cheol H.
AU - Kinoshita, Masahiko
AU - Matsuda, Yuzuru
AU - Aarhus, Lawrence L.
AU - Burnett, John C.
AU - Miller, Wayne L.
N1 - Funding Information:
This study was supported in part by grants from the American Heart Association, Minnesota Affiliate, Minneapolis, Minnesota; the National Heart, Lung, and Blood Institute (Grant HL-033643), National Institutes of Health, Bethesda, Maryland; and the Mayo Foundation, Rochester, Minnesota.
PY - 1996/10
Y1 - 1996/10
N2 - 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.
AB - 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.
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U2 - 10.1016/S0735-1097(96)00241-0
DO - 10.1016/S0735-1097(96)00241-0
M3 - Article
C2 - 8837586
AN - SCOPUS:0030273511
SN - 0735-1097
VL - 28
SP - 1031
EP - 1038
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 4
ER -