title: Hyperosmolality-mediated peritoneal microvascular vasodilation is linked to aquaporin function.
abstract: Glucose-based peritoneal dialysis (PD) solutions dilate the parietal and visceral peritoneal microvasculature by endothelium-dependent mechanisms that primarily involve hyperosmolality. This PD-mediated dilation occurs by active intracellular glucose uptake and adenosine Al receptor activation, and by hyperosmolality-stimulated glibenclamide-sensitive potassium channels. Both pathways invoke NO as a second messenger for vasodilation. We hypothesized that during crystalloid-induced osmosis, the osmotic water flux through the transendothelial water-exclusive aquaporin 1 (AQP1) channels is the primary mechanism whereby the endothelium is being stimulated to instigate hyperosmolality-driven vasodilation. Four microvascular levels (diameters in the range 6 - 100 microm) were visualized by intravital videomicroscopy of the terminal ileum in anesthetized rats. Microvascular diameters and flow were measured after topical exposure to a 5% hypertonic mannitol or 2.5% glucose-based PD solution, at baseline and after brief tissue pre-treatment (with 0.1% glutaraldehyde for 10 seconds) or after combined tissue pre-treatment and pharmacologic blockade of AQP1 with HgCl2 (100 micromol/L). Vascular endothelial integrity was verified by the response to acetylcholine (10(-4) mol/L) and sodium nitroprusside (10(-4) mol/L). The hyperosmolar solutions both caused rapid and sustained vasodilation at all microvascular levels, which was not altered by tissue pre-treatment. Inhibition of AQP1 completely abolished the mannitol-induced vasodilation and markedly attenuated the PD fluid-mediated vasodilation. Neither glutaraldehyde pre-treatment nor HgCl2 affected tissue integrity or endothelial cell function. We conclude that the peritoneal microvascular vasodilation caused by hyperosmolar PD fluid is instigated by the osmotic water flux through AQP1. Clinical PD solutions have components other than hyperosmolality that can induce endothelium-dependent peritoneal microvascular vasodilation independent of the AQP1-mediated osmosis.
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: Asma
authors.initials: A
authors.lastname: Althani
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Fawzi
authors.forename: Omar M
authors.initials: OM
authors.lastname: Fituri
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D000077324:Crystalloid Solutions; D015314:Dialysis Solutions / Q000493:pharmacokinetics*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D005947:Glucose / Q000493:pharmacokinetics*; D005976:Glutaral / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008627:Mercuric Chloride / Q000494:pharmacology; D009995:Osmosis; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000077324:Crystalloid Solutions; D015314:Dialysis Solutions; D004234:Diuretics, Osmotic; D007552:Isotonic Solutions; D051398:Aquaporin 1; D008353:Mannitol; D008627:Mercuric Chloride; D005947:Glucose; D005976:Glutaral