Effect of losartan on gene expression of type 2 angiotensinII receptor and inducible nitric oxide synthase in diabetic rat renal cortex

AIM To investigate effect of losartan on angiotensin and nitric oxide system in diabetic rats kidney,and to elucidate the relation between them.METHODS Rats were randomly divided into 3 groups: control group,diabetic model group and losartan(30 mg·kg~(-1)·d~(-1)×8 weeks,ig) group.mRNA expressions of type 2 angiotensinⅡ receptor (AT_2),collagen Ⅳ and inducible nitric oxide synthase((iNOS)) in renal cortex were measured by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) respectively.In addition,nitric oxide synthase(NOS) activity,the level of angiotensin Ⅱ and NO in renal cortex were also determined.RESULTS In diabetic model group,urine protein excretion,renal angiotensinⅡ level,collagen Ⅳ mRNA and iNOS mRNA expression were increased obviously as compared to control group.Activity of NOS in diabetic model group was increased,too.However,NO level and AT_2 mRNA expression showed a significant decrease as compared to control group.Administration of losartan markedly ameliorated urine protein excretion and collagen Ⅳ mRNA expressions,but increased NOS activity,NO level,AT_2 mRNA expression and iNOS mRNA expression in renal cortex obviously as compared to diabetes group.CONCLUSION Activation of AT_2 is related to the renal protective roles of losartan,and may involve in the up-regulation of iNOS(mRNA) expression in kidney.