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Disparity in Osmolarity-Induced Vascular Reactivity

El Rasheid Zakaria^*,, C. Michelle Hunt^*, Na Li^*, Patrick D. Harris^* and R. Neal Garrison^*,,

Departments of ^* Physiology and Biophysics and Surgery, University of Louisville, and Veterans Administration Medical Center, Louisville, Kentucky

Address correspondence to: Dr. El Rasheid Zakaria, Department of Physiology and Biophysics, Health Sciences Center A-1115, University of Louisville, Louisville, KY 40292. Phone: 502-287-5249; Fax: 502-894-6242; E-mail: erzaka01{at}louisville.edu

Received for publication September 13, 2004. Accepted for publication June 24, 2005.

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 ± 0.2% of baseline), which was not observed in the larger inflow arterioles (100 µm). This isotonic glucose–mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A_2a and A_2b receptor antagonists and completely abolished by adenosine A₁ receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes’ metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor–mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673