THE EFFECT OF COOLING ON THE CONTRACTILE RESPONSE TO ENDOTHELIN-1 IN SMALL ARTERIES FROM HUMANS

The pathogenesis of the prolonged cold-induced vasospasm of Raynaud's disease (RD) is unknown. Cooling has been shown to decrease the sensitivity of cutaneous rabbit ear arteries to endothelin-1 (ET-1), perhaps by increasing the availability of nitric oxide (NO). If the endothelium in RD lacks this NO-mediated inhibitory function during cooling, increased production and enhanced constriction to ET-1 could cause vasospasm. This study examined the effect of cooling on the contractile response to ET-1 in human microvessels. Small arteries were dissected from biopsy specimens of human fat and were cannulated in a small vessel arterio-graph. Cumulative concentration-response curves to ET-1 (10(-12) to 3 x 10(-7) M) were obtained in vessels at 37 degrees C (n = 8) and 24 degrees C (n = 7). Cooling to 24 degrees C resulted in an eightfold decrease in sensitivity to ET-1 (EC(50) 6.6 +/- 2.5 x 10(-10) M at 37 degrees C vs. 5.5 +/- 2.5 x 10(-9) M at 24 degrees C; p <0.05, unpaired t test). The E(max) was not significantly different at 37 degrees C and 24 degrees C (114 +/- 9 at 37 degrees C vs. 138 +/- 14 at 24 degrees C; p = 0.18). These results suggest that cooling decreases the sensitivity of human microvessels to ET-1. Further investigation is needed to establish the mechanism of this effect, including studies in vessels obtained from patients with RD.