Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries. J Appl Physiol (1985) 2002 Oct;93(4):1391-9
Date
09/18/2002Pubmed ID
12235040DOI
10.1152/japplphysiol.00247.2002Scopus ID
2-s2.0-0036785969 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
In contrast to its constrictor effects on peripheral arteries, 20-hydroxyeicosatetraenoic acid (20-HETE) is an endothelial-dependent dilator of pulmonary arteries (PAs). The present study examined the hypothesis that the vasodilator effects of 20-HETE in PAs are due to an elevation of intracellular calcium concentration ([Ca(2+)](i)) and the release of nitric oxide (NO) from bovine PA endothelial cells (BPAECs). BPAECs express cytochrome P-450 4A (CYP4A) protein and produce 20-HETE. 20-HETE dilated PAs preconstricted with U-46619 or norepinephrine and treated with the cytochrome P-450 inhibitor 17-octadecynoic acid and the cyclooxygenase inhibitor indomethacin. The dilator effect of 20-HETE was blocked by the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) or by removal of endothelium. 20-HETE significantly increased [Ca(2+)](i) and NO production in BPAECs. 20-HETE-induced NO release was blunted by removal of extracellular calcium, as well as NO synthase inhibitors (L-NAME). These results suggest that 20-HETE dilates PAs at least in part by increasing [Ca(2+)](i) and NO release in BPAECs.
Author List
Yu M, McAndrew RP, Al-Saghir R, Maier KG, Medhora M, Roman RJ, Jacobs ERAuthors
Elizabeth R. Jacobs MD Emeritus Professor in the Medicine department at Medical College of WisconsinMeetha Medhora Professor in the Radiation Oncology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Cattle
Cells, Cultured
Cytochrome P-450 CYP4A
Cytochrome P-450 Enzyme System
Endothelium, Vascular
Hydroxyeicosatetraenoic Acids
Intracellular Membranes
Mixed Function Oxygenases
Nitric Oxide
Osmolar Concentration
Pulmonary Artery
Vasodilation
Vasodilator Agents
