Impaired cholinergic dilator response of resistance arteries isolated from patients with Raynaud's disease.

Abstract

We examined the effect of cooling on the response to the endothelium-dependent and -independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud's disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD. Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age-and sex-matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, 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 SNP (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). Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37 degrees C (Emax=45+/-13 in RD vs 89+/-4 in controls; P=0.004). These results support the hypothesis that impaired endothelium-dependent vasodilatation is involved in the pathophysiology of RD.