title: Physiopathological implications of P2X1and P2X7receptors in regulation of glomerular hemodynamics in angiotensin II-induced hypertension.
abstract: Deleterious effects of purinergic P2X1and P2X7receptors (P2XRs) in ANG II-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2X1R, P2X7R, and P2X4R with NF449, A438079, and PSB12054, respectively, were evaluated in ANG II-infused rats (435 ng·kg-1·min-1). P2X1R or P2X7R blockade reduced afferent (6.85 ± 1.05 vs. 2.37 ± 0.20 dyn·s-1·cm-5) and efferent (2.85 ± 0.38 vs. 0.99 ± 0.07 dyn·s-1·cm-5) arteriolar resistances, leading to increases in glomerular plasma flow (75.82 ± 5.58 vs. 206.7 ± 16.38 nl/min), ultrafiltration coefficient (0.0198 ± 0.0024 vs. 0.0512 ± 0.0046 nl·min-1·mmHg-1), and single-nephron glomerular filtration rate (22.73 ± 2.02 vs. 51.56 ± 3.87 nl/min) to near normal values. Blockade of P2X4R did not elicit effects in hypertensive rats. In normotensive sham-operated rats, only the P2X1R antagonist caused an increase plasma flow and single-nephron glomerular filtration rate, whereas the P2X4R antagonist induced glomerular vasoconstriction that was consistent with evidence that P2X4R stimulation increases release of nitric oxide from endothelial cells. Mean arterial pressure remained unchanged in both hypertensive and normotensive groups. Western blot analysis showed overexpression of P2X1R, P2X7R, and P2X4R proteins in hypertensive rats. Whereas it has been generally assumed that the altered glomerular vascular resistances in ANG II hypertension are due to AT1receptor-mediated vasoconstriction, these data indicate a predominant P2X1R and P2X7R control of glomerular hemodynamics in ANG II hypertension.
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México; marthafranco@lycos.com.
authors.forename: Martha
authors.identifier: 0000-0003-4073-524X
authors.initials: M
authors.lastname: Franco
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México.
authors.forename: Rocío
authors.initials: R
authors.lastname: Bautista-Pérez
authors.affiliation: Department of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México.
authors.forename: Agustina
authors.initials: A
authors.lastname: Cano-Martínez
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México.
authors.forename: Ursino
authors.initials: U
authors.lastname: Pacheco
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México.
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.affiliation: Pharmacology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México; and.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Del Valle Mondragón
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez," México City, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Pérez-Méndez
authors.affiliation: Department of Physiology and Hypertension and Renal Center, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000804:Angiotensin II; D000818:Animals; D062186:Arterial Pressure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D017208:Rats, Wistar; D058474:Receptors, Purinergic P2X1 / Q000187:drug effects / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4 / Q000187:drug effects / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D017595:Renal Plasma Flow; D015398:Signal Transduction; D014661:Vasoconstriction
chemical_list: C548228:P2rx4 protein, rat; C546470:P2rx7 protein, rat; D058920:Purinergic P2X Receptor Antagonists; D058474:Receptors, Purinergic P2X1; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D000804:Angiotensin II; D009569:Nitric Oxide
keywords: ATP; P2X antagonists; angiotensin II-induced hypertension; glomerular hemodynamics