期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 294, 期 1, 页码 F161-F169出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00281.2007
关键词
extracellular ATP; renal inflammation; vascular hypertrophy
资金
- NCRR NIH HHS [P20-RR-017659, P20 RR017659] Funding Source: Medline
- NHLBI NIH HHS [HL-26371, R01 HL026371] Funding Source: Medline
- NIDDK NIH HHS [R01 DK072408, R01 DK072408-01A1] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017659] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL026371] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK072408] Funding Source: NIH RePORTER
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. alpha-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. alpha-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/mm(2)) and tubular proliferation (71 +/- 15 vs. 20 +/- 4 cell/mm(2)) and these effects were prevented by clopidogrel (52 +/- 4 and 36 +/- 3 cell/mm(2)) 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.
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