Endothelium-dependent relaxation of small resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease

Impaired endothelium-dependent relaxation has been demonstrated previously in resistance vessels of Han:SPRD polycystic kidney disease rats. The aim o f the present study was to investigate whether endothelium-dependent relaxa tion is reduced also in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether this is influenced by the nitric oxide (NO) sys tem. Small subcutaneous resistance vessels from normotensive ADPKD patients with normal or near-normal renal function (n = 9) and from healthy control subjects (n = 10) were mounted in a Mulvany-Halpern myograph. The morpholo gy of the vessels and acetylcholine (ACh)-induced endothelium-dependent rel axation, as well as 3-morpholino-sydnonimine (SIN-1, NO donor)-induced endo thelium-independent relaxation were investigated. The results showed that: (1) there were no significant differences in morphologic parameters of resi stance vessels between the two groups; (2) the maximal ACh-induced relaxati on rate was decreased in ADPKD patients compared with control subjects (71. 5 +/- 12.1 versus 85.2 +/- 8.7%, P < 0.01); (3) in the presence of L-argini ne (a substrate of NO synthase), a left shift of the ACh dose-response curv es was found in control subjects, but not in ADPKD patients; (4) in the pre sence of the N-G-nitro-L-arginine methyl ester (an inhibitor of NO synthase ), a right shift of the ACh dose-response curve was found in control subjec ts, but not in ADPKD patients; and (5) endothelium-independent relaxation r ate induced with SIN-1 was similar in patients and control subjects. In con clusion, endothelium-dependent relaxation was impaired in resistance vessel s from patients with ADPKD. The reduced response of the vessels to both the substrate and inhibitor of NO synthase in ADPKD suggests that an impairmen t of NO synthase may be involved in the mechanism of endothelial dysfunctio n in ADPKD.