The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD

Abstract

Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.

Mice that Lack Endothelial Nitric Oxide Synthase Are Protected against Functional and Structural Modifications Induced by Acute Peritonitis

“…Addition of the NO donor nitroprusside to the dialysate increases EPSA in rat models (23) and stable PD patients (24). An increased release of NO is also involved in the increased EPSA and the loss of UF that are observed during acute peritonitis (25).…”

Disparity in Osmolarity-Induced Vascular Reactivity

“…With dissipation of the osmotic gradient with time as a result of glucose absorption, a subordinate vasodilation is preferentially maintained in the smaller intestinal premucosal A3, whereas the feed A1 at most restore their baseline diameter and blood flow, which explains the relatively lower PS for small solutes during the late phase of the dwell. In contrast, in peritoneal transport rate studies in humans, the addition of a clinical dose of sodium nitroprusside to a dialysis solution produced no effect on peritoneal fluid kinetics, a slight increase in MTAC for small solutes, but a great increase in macromolecular clearances (35). Similarly, in rabbits, a clinical dose of sodium nitroprusside exclusively enhanced peritoneal macromolecular clearance (36).…”

Similarities and Differences between the Effects of Amino Acids and Nitroprusside on Peritoneal Permeability during CAPD

“…Although one of the amino acids of this dialysate was L-arginine, a substrate for nitric oxide synthesis, the effects of the amino acid solution could not be attributed to nitric oxide synthesis. Intraperitoneal administration of the nitric oxide donor nitroprusside also caused changes in permeability characteristics [6]. These changes were accompanied by local generation of cyclic guanosine monophosphate, the second messenger of nitric oxide synthesis.…”