Roles of mitogen-activated protein kinases and angiotensin II in renal development

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT1) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-week-old angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT1 and type 2 AII (AT2) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

Effects of angiotensin II receptor antagonist on remodeling of renal arterioles in hypertension / 中国病理生理杂志

AIM: To investigate the effects of angiotensin II receptor antagonist on remodeling of renal arterioles in hypertension. METHODS: Eighteen 4 weeks old male rats were divided into three groups: Wistar-Kyoto rats (WKY) for normotensive group, and spontaneously hypertensive rats (SHR) for hypertensive group, and SHR treated with losartan orally (15 mg?kg -1 ?d -1 ). The rats were raised to 16 weeks old. The morphometric parameters of the renal arterioles, and the widths of vascular smooth muscle cells (VSMC) and intercellular space were studied on kidney slices by light microscope and electromicroscope respectively, combined with computer-assistant image analysis system. The minimal renal vascular resistance (RVR min ) was studied by isolated kidney perfusion system. RESULTS: The systolic blood pressure of the tail artery, wall thickness, wall area, ratio of wall thickness to inner diameter, width of VSMC of renal arterioles and RVR min were all smaller or lower in losartan group than those of SHR. CONCLUSION: Ang II receptor antagonist losartan can prevent the remodeling of renal arterioles in SHR.