Peritoneal dialysis solutions contract arteries through endothelium-independent prostanoid pathways

Conventional peritoneal dialysis solution (PDS) relaxes visceral and parietal peritoneal arterioles (microvessels) by unclear mechanisms. The present study was originally designed to investigate the mechanisms of PDS-mediated vascular reactivity. Surprisingly, our preliminary data indicated that PDS induces contraction in large vessels such as the aorta. That result contrasts with the relaxation observed in the microvasculature. We therefore extended the study to (1) determine the effect of PDS on the superior mesenteric artery (SMA), (2) confirm the PDS-induced contraction in the aorta, and (3) determine if a prostanoid and nitric oxide are involved in the observed PDS-induced vessel response. Rat SMA rings with intact endothelium and aortic rings with and without endothelium were prepared and placed in baths filled with a non vasoactive physiologic salt solution (PSS), or with PSS plus mefenamic acid (MFA, a cyclo-oxygenase inhibitor), or PSS plus NG-monomethyl-L-arginine (L-NMMA, an inhibitor of nitric oxide synthase) under a force transducer. We recorded changes in tension throughout the protocols. After equilibration, the baths were filled with a conventional glucose-based PDS (Delflex 2.5%: Fresenius Medical Care, Bad Homburg, Germany) with and without MFA or L-NMMA for 30 minutes. The rings were then washed, contracted with phenylephrine, and relaxed with acetylcholine to verify the presence or absence of endothelium. In both SMA and aorta, PDS induced contraction. That contraction was suppressed by MFA [SMA: 0.57 g vs. 0.13 g (+/- 0.035 g); aorta: 0.88 g vs. 0.27 g (+/- 0.035 g); p < 0.05 by analysis of variance (ANOVA)]. Aortic contraction induced by PDS was not altered by L-NMMA. Conventional PDS induces contraction in large vessels, in contrast to its action of relaxation in microvessels. Vascular reactivity in large vessels involves the production of a constrictor prostanoid in the vascular smooth muscle. Peritoneal dialysis solutions do not induce NO in aortic endothelium. Peritoneal dialysis solution-induced, prostanoid-mediated contraction of smooth muscle may contribute to a worsening of hypertension and the premature uterine contractions observed in the rare cohort of pregnant uremic patients on peritoneal dialysis.