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 F2α, 2 × 10−6 M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro (“organ chambers”) exposed to progressive hypothermia (from 37 to 10 °C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI2 and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 °C. This vasodilatation began at 35 °C and, in the presence of indomethacin (2 × 10−6 M), at 30 °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 (2 × 10−6 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 PGI2 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.