RT Journal Article
SR Electronic
T1 Endothelium-Derived Nitric Oxide Inhibits the Relaxation of the Porcine Coronary Artery to Natriuretic Peptides by Desensitizing Big Conductance Calcium-Activated Potassium Channels of Vascular Smooth Muscle
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 223
OP 231
DO 10.1124/jpet.110.166652
VO 334
IS 1
A1 Chao Fan Liang
A1 Alice Lai Shan Au
A1 Susan Wai Sum Leung
A1 Kwok Fu Jacobus Ng
A1 Michel Félétou
A1 Yiu Wa Kwan
A1 Ricky Ying Keung Man
A1 Paul M. Vanhoutte
YR 2010
UL http://jpet.aspetjournals.org/content/334/1/223.abstract
AB The present experiments investigated whether endothelium-derived mediators modulate the effect of natriuretic peptides in porcine coronary arteries. Rings with and without endothelium were suspended in organ chambers for isometric tension recording. Concentration-relaxation curves to C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) were obtained during contractions to endothelin-1. Removal of the endothelium potentiated relaxations to both CNP and ANP. Nω-nitro-l-arginine methyl ester potentiated relaxations to natriuretic peptides only in arteries with endothelium. Sodium nitroprusside (SNP) inhibited the response to the natriuretic peptides only in the absence of the endothelium. In rings with endothelium, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (NS2028) potentiated CNP-mediated relaxations. Iberiotoxin (IBTX) reduced the response only in rings without endothelium. Glybenclamide inhibited the relaxations in both the presence and absence of endothelium. CNP-induced relaxations were reduced by 8-bromoguanosine 3′,5′-cGMP (8-bromo-cGMP) to the same extent in rings with and without endothelium. There was no significant difference between the increased cGMP content caused by CNP in porcine coronary arteries with or without endothelium. In patch-clamp studies in porcine coronary arterial smooth muscle cells, the natriuretic peptide-mediated enhancement of the IBTX-sensitive big conductance calcium-activated potassium channel (BKCa) amplitude was reversed by SNP and 8-bromo-cGMP. These findings demonstrate that, in the porcine coronary artery, the opening of BKCa and ATP-dependent potassium channels of the vascular smooth muscle contributes to CNP-mediated relaxations. Endothelium-derived and exogenous NO inhibit the direct relaxing effect of natriuretic peptides by desensitizing the response of the BKCas of the vascular smooth muscle to the generation of cGMP. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics