• Malwina Monika Roszkowska-Chojecka, Agnieszka Walkowska, Janusz Sadowski, and Leszek Dobrowolski.
• Department of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
• Am. J. Med. Sci. 2018 Sep 1; 356 (3): 287-295.

BackgroundAdenosine-5'-diphosphate (ADP) can influence intrarenal vascular tone and tubular transport, partly through activation of purine P2Y12 receptors (P2Y12-R), but their actual in vivo role in regulation of renal circulation and excretion remains unclear.MethodsThe effects of intravenous ADP infusions of 2-8mg/kg/hour were examined in anesthetized Wistar rats that were untreated or chronically pretreated with clopidogrel, 20mg/kg/24hours, a selective P2Y12-R antagonist. Renal blood flow (transonic probe) and perfusion of the superficial cortex and medulla (laser-Doppler fluxes) were measured, together with urine osmolality (Uosm), diuresis (V), total solute (UosmV), sodium (UNaV) and potassium (UKV) excretion.ResultsADP induced a gradual, dose-dependent 15% decrease of mean arterial pressure, a sustained increase of renal blood flow and a 25% decrease in renal vascular resistance. Clopidogrel pretreatment attenuated the mean arterial pressure decrease, and did not significantly alter renal blood flow or renal vascular resistance. Renal medullary perfusion was not affected by ADP whereas Uosm decreased from 1,080 ± 125 to 685 ± 75 mosmol/kg H20. There were also substantial significant decreases in UosmV, UNaV and UKV; all these changes were attenuated or abolished by clopidogrel pretreatment. Two-weeks' clopidogrel treatment decreased V while UosmUosmV and UNaV increased, most distinctly after 7 days. Acute clopidogrel infusion modestly decreased mean arterial pressure and significantly increased outer- and decreased inner-medullary perfusion.ConclusionsOur functional studies show that ADP can cause systemic and renal vasodilation and a decrease in mean arterial pressure, an action at least partly mediated by P2Y12 receptors. We confirmed that these receptors exert tonic action to reduce tubular water reabsorption and urine concentration.Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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