HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/F161    most recent 00281.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Graciano, M. L. Articles by Navar, L. G. Search for Related Content PubMed PubMed Citation Articles by Graciano, M. L. Articles by Navar, L. G.

Purinergic receptors contribute to early mesangial cell transformation and renal vessel hypertrophy during angiotensin II-induced hypertension

¹Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans; ²Department of Internal Medicine, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, Brazil; ³Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan; ⁴Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, Louisiana; and ⁵Division of Natural Sciences, University of California, Merced, California

Submitted 21 June 2007 ; accepted in final form 2 November 2007

Chronic ANG II infusions lead to increases in intrarenal ANG II levels, hypertension, and tissue injury. Increased blood pressure also elicits increases in renal interstitial fluid (RIF) ATP concentrations that stimulate cell proliferation. We evaluated the contribution of purinergic receptor activation to ANG II-induced renal injury in rats by treating with clopidogrel, a P2Y12 receptor blocker, or with PPADS, a nonselective P2 receptor blocker. -Actin expression in mesangial cells, afferent arteriolar wall thickness (AAWT), cortical cell proliferation, and macrophage infiltration were used as early markers of renal injury. Clopidogrel and PPADS did not alter blood pressure, renin or kidney ANG II content. -Actin expression increased from control of 0.6 ± 0.4% of mesangial area to 6.3 ± 1.9% in ANG II-infused rats and this response was prevented by clopidogrel (0.4 ± 0.2%) and PPADS. The increase in AAWT from 4.7 ± 0.1 to 6.0 ± 0.1 mm in ANG II rats was also prevented by clopidogrel (4.8 ± 0.1 mm) and PPADS. ANG II infusion led to interstitial macrophage infiltration (105 ± 16 vs. 62 ± 4 cell/mm²) and tubular proliferation (71 ± 15 vs. 20 ± 4 cell/mm²) and these effects were prevented by clopidogrel (52 ± 4 and 36 ± 3 cell/mm²) and PPADS. RIF ATP levels were higher in ANG II-infused rats than in control rats (11.8 ± 1.9 vs. 5.6 ± 0.6 nmol/l, P < 0.05). The results suggest that activation of vascular and glomerular purinergic P2 receptors may contribute to the mesangial cell transformation, renal inflammation, and vascular hypertrophy observed in ANG II-dependent hypertension.

extracellular ATP; renal inflammation; vascular hypertrophy