Cytosolic Phospholipase A2? Is Essential for Renal Dysfunction and End-Organ Damage Associated With Angiotensin II-Induced Hypertension.

ABSTRACT: The kidney plays an important role in regulating blood pressure (BP). cPLA2? in the kidney is activated by various agents including angiotensin II (Ang II) and selectively releases arachidonic acid (AA) from tissue lipids, generating pro- and antihypertensive eicosanoids. Since activation of cPLA2? is the rate-limiting step in AA release, this study was conducted to determine its contribution to renal dysfunction and end-organ damage associated with Ang II-induced hypertension.cPLA2?(+/+) and cPLA2?(-/-) mice were infused with Ang II (700 ng/ kg/min) or its vehicle for 13 days. Mice were placed in metabolic cages to monitor their food and water intake, and urine was collected and its volume was measured. Doppler imaging was performed to assess renal hemodynamics. On the 13th day of Ang II infusion, mice were sacrificed and their tissues and blood collected for further analysis.Ang II increased renal vascular resistance, water intake, and urine output and Na(+) excretion, decreased urine osmolality, and produced proteinuria in cPLA2?(+/+) mice. Ang II also caused accumulation of F4/80(+) macrophages and CD3(+) T cells and renal fibrosis, and increased oxidative stress in the kidneys of cPLA2?(+/+) mice. All these effects of Ang II were minimized in cPLA2?(-/-) mice.cPLA2? contributes to renal dysfunction, inflammation, and end-organ damage, most likely via the action of pro-hypertensive eicosanoids and increased oxidative stress associated with Ang II-induced hypertension. Thus, cPLA2? could serve as a potential therapeutic target for treating renal dysfunction and end-organ damage in hypertension.

SUBMITTER: Khan NS 

PROVIDER: S-EPMC4751243 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature