RESPONSE OF RABBIT EAR ARTERY TO ENDOTHELIN-1 DURING COOLING

1 The effects of cooling on the response of rabbit central ear artery to endothelin-1 and the role of the endothelium in these effects were studied in 2 mm long cylindrical arterial segments. 2 Concentration-response curves for endothelin-1 (10(-10)-3 x 10(-7) M) were recorded isometrically in arteries with and without endothelium at 37-degrees-C and during cooling (24-degrees-C). To analyze further the endothelial mechanisms of the response to endothelin-1 during cooling, the effects of this peptide in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) or meclofenamate (10(-5) M) were also determined. 3 In every condition tested, endothelin-1 produced a marked, concentration-dependent arterial contraction. Sensitivity of intact arteries to this peptide was consistently lower at 24-degrees-C than at 37-degrees-C. At 37-degrees-C there were comparable responses of arteries with and without endothelium, but at 24-degrees-C arteries without endothelium showed a higher sensitivity than intact arteries to endothelin-1. 4 L-NAME (10(-4) M) increased the maximal contraction at 37-degrees-C, and both the sensitivity and maximal contraction at 24-degrees-C of intact arteries to endothelin-1. Meclofenamate (10(-5) M) did not affect the arterial response to endothelin-1. 5 Sensitivity of arteries with and without endothelium to nitroprusside (10(-9)-10(-3) M) was significantly decreased during cooling, and endothelium removal did not affect the relaxation to this nitrovasodilator. 6 These results suggest that cooling decreases sensitivity of cutaneous arteries (ear artery) to endothelin-1 probably by increasing the availability of endothelial nitric oxide.