Nitric oxide and prostaglandins mediate vasodilation to 5,6-EET in rabbit lung.
We have previously found that 5,6-EET (epoxyeicosatrienoic acid)(50 nM) significantly dilates the vascular bed(42%) of the isolated, constantly perfused rabbit lung, which has been constricted with U46619(5-8 pM). We studied the role of EDRF-NO and prostaglandins in the 5,6-EET-induced vascular relaxation. Dilation to 5,6-EET was evident only when the pulmonary vascular tone was increased. L-NNA (N omega-nitro-L-arginine, 10(-4) M), an inhibitor of NO synthase(NOS); U46619(5-10 pM), a thromboxane mimetic; and L-NNA + INDO(indomethacin, 10(-5) M), a cyclooxygenase inhibitor, all increased the pressure of pulmonary artery(PPa) from baseline, to a peak range of 28-38mmHg(32.75 [symbol: see text] 2.2), whereas INDO alone increased Ppa only by 10mmHg. L-NNA + INDO,L-NNA alone, and INDO + U46619 attenuated the 5,6-EET relaxing effect by 100%, 88% and 64.5%, respectively. In the presence of L-NNA and 5,6-EET, SNAP(S-nitroso-N-acetyl-D,L-penicillamine, 10(-6) M), a NO donor, reduced Ppa by 75%. We conclude that the mechanism of vasodilation to 5,6-EET in the rabbit pulmonary circulation is via both EDRF-NO and PG pathways and that the vasodilation is largely EDRF-NO dependent.
Tan
J Z
JZ
Department of Physiology, New York Medical College, Valhalla 10595, USA.
Kaley
G
G
Gurtner
G H
GH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid