Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia.
Nitric oxide and prostacyclin are endogenous endothelium-derived vasodilators, but little information is available on their release during hypothermia. This study was carried out to test the hypothesis that endothelium may modulate vascular reactivity to decreased temperature changes. Segments of contracted (prostaglandin F(2alpha), 2x10(-6)M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro ("organ chambers") exposed to progressive hypothermia (from 37 to 10 degrees C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI(2) and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 degrees C. This vasodilatation began at 35 degrees C and, in the presence of indomethacin (2x10(-6)M), at 30 degrees C. Endothelium-dependent vasodilatation to hypothermia was blocked by L-NMMA or L-NOARG (10(-5)M), two competitive inhibitors of nitric oxide synthase (n=5 each, P<0.05). Oxyhemoglobin (2x10(-6)M) also inhibited vasodilatation induced by hypothermia (n=6, P<0.05). Pretreatment with either atropine or pirenzepine (10(-6)M) inhibited hypothermia-mediated vasodilatation (n=5 each, P<0.05). The present in vitro study concluded that the endothelium is sensitive to temperature variations and indicated that PGI(2) and NO-dependent pathways may be involved endothelium-dependent relaxation to hypothermia. The endothelium-dependent vasodilatation to hypothermia, in systemic and coronary arteries, is mediated by the M1 muscarinic receptor.
Evora
Paulo R B
PR
Ribeirão Preto Faculty of Medicine, University of Sao Paulo, Department of Surgery and Anatomy, Rua Rui Barbosa, 367, Apt. 15, 14015-120, Ribeirao Preto, SP, Brazil. prbevora@netsite.com.br
Cable
David G
DG
Chua
Yeow L
YL
Rodrigues
Alfredo J
AJ
Pearson
Paul J
PJ
Schaff
Hartzell V
HV
D000818:Animals; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D013696:Temperature
D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D011464:Epoprostenol; D007213:Indomethacin