Prior episode of anoxia attenuates vasorelaxation in response to subsequent episode of anoxia.
To examine the effect of a prior episode of anoxia on subsequent anoxia-mediated vasorelaxation, norepinephrine-precontracted endothelium-intact rat aortic rings were first exposed to anoxia (95% N2-5% CO2 for 5, 15, or 30 min) then to normoxia (95% O2-5% CO2 for 15 min). These rings were exposed again to anoxia for 30 min. First exposure of rings to anoxia for 30 min resulted in 77 +/- 4% decrease in tone (vasorelaxation), whereas second exposure resulted in only 10 +/- 4% relaxation (n = 11, P < 0.001 vs. relaxation during first exposure). First exposure of rings to anoxia for 5 or 15 min also diminished relaxation to 59 +/- 3 and 19 +/- 8%, respectively, on second exposure to anoxia (both P < 0.01 vs. relaxation during 1st anoxia). Attenuation of vasorelaxation by prior episode of anoxia was not affected by treatment of rings with indomethacin (10(-5) M), the Ca2+ channel blocker felodipine (10(-6) M), the superoxide anion scavenger superoxide dismutase (100 micrograms/ml), or adenosine A1 and A2 blockers (each 10(-6) M). To examine the role of intact functional endothelium in attenuation of vasorelaxation during second anoxic exposure, rings were deendothelialized and treated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) or the guanylate cyclase inhibitor methylene blue (MB; 2 x 10(-5) M). In all deendothelialized rings, vasorelaxation during second anoxic exposure was similar to that during first anoxic exposure (100 +/- 0 vs. 98 +/- 3%, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
B C
BC
Department of Medicine, University of Florida, Gainesville.
Mehta
J L
JL
D000241:Adenosine / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology; D005609:Free Radicals; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D012008:Recurrence; D014664:Vasodilation; D019323:omega-N-Methylarginine
D005609:Free Radicals; D058915:Purinergic P1 Receptor Antagonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D011451:Prostaglandin-Endoperoxide Synthases; D000241:Adenosine; D002118:Calcium