Impaired cholinergic dilator response of resistance arteries isolated frompatients with Raynaud's disease

Aims We examined the effect of cooling on the response to the endothelium-d ependent and -independent dilators, acetylcholine (ACh) and sodium nitropru sside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud's disease (RD) patients and controls, in order t o assess the pathogenic role of the endothelium in RD. Methods Subcutaneous resistance arteries were dissected from gluteal fat bi opsies taken from patients with RD (n = 18) and h-om age-and sex-matched co ntrol subjects (n = 17). Vessels were cannulated in a small vessel arteriog raph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration response curves for ACh (10(-10)-10(-4) M) and SN P (10(-10)-10(-3) M) were generated in vessels at either 37 degrees C or 24 degrees C, with endothelium intact for ACh and removed for SNP (n = 6 per group). Results Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at eithe r temperature, but the maximal relaxation to ACh was depressed in vessels f rom RD patients compared with controls at 37 degrees C (E-max = 45 +/- 13 i n RD vs 89 +/- 4 in controls; P = 0.004). Conclusions These results support the hypothesis that impaired endothelium- dependent vasodilatation is involved in the pathophysiology of RD.