Molecular Mechanisms of Peritoneal Dialysis–Induced Microvascular Vasodilation
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Peritoneal dialysis (PD) solutions dilate microvessels by undefined mechanisms. This vasodilation directly affects ultrafiltration and solute exchange during a PD dwell and is thought to account for the variable mass transfer area coefficient for small solutes during a glucose-based hypertonic dwell. We hypothesized that PD-mediated vasodilation occurs by endothelium-dependent mechanisms that involve endothelium energy-dependent K+ channels (KATP), adenosine A1 receptor activation, and NO release. We used intravital videomicroscopy to study 3 levels of microvessels (A1 inflow arterioles about 100 μm diameter to pre-capillary A3 arterioles 10 – 15 μm diameter) in the terminal ileum of anesthetized rats under control conditions in vivo in a tissue bath. Ileum was bathed with hypertonic mannitol or 2.5% glucose-based PD solution (Delflex: Fresenius Medical Care North America, Waltham, MA, U.S.A.) with or without topical application of individual or combined specific inhibitors of the endotheliumdependent dilation pathways: NO (L-NMMA), prostaglandin I2 (mefenamic acid), endothelium hyperpolarizing factor (glibenclamide), and adenosine A1 receptor antagonist (DPCPX). The mannitol and PD solutions induced rapid and sustained peritoneal vasodilation whose magnitude depended on microvascular level and osmotic solute. Combined inhibition of endothelium-dependent dilation pathways completely abolished the mannitolinduced hyperosmolality-mediated dilation at all microvascular levels, but selectively eliminated the PD solution–mediated A3 dilation. The KATP and adenosine receptor antagonists, individually or combined, remarkably attenuated dilation in the smaller pre-capillary arterioles; NO inhibition, alone or combined with KATP and adenosine receptor antagonists, eliminated the PD solution–induced dilation. The cyclooxygenase pathway is not involved in PD-induced dilation. Solutions for PD dilate the visceral peritoneal microvasculature by endothelium-dependent mechanisms, primarily the NO pathway. Adenosine receptor–activated NO release and KATP channelmediated endothelium hyperpolarization significantly contribute to vasodilation in the smaller peritoneal pre-capillary arterioles.
- Health Sciences-CAS (pre 2016) [123 items ]