Effect of angiotensin II receptor blockade on Janus kinases-signal transducers and activators of transcription in renal tissues in hypertensive

Abstract

Objective To observe the effects of irbesartan, an angiotensin Ⅱ receptor blocker, on the protein expression of janus kinases-signal transducers and activators of transcription (JAKs-STATs) in kidneys in hypertension and to evaluate the role of the JAKs-STATs pathway in hypertension with renal injury. Methods Twelve spontaneously hypertension rats (SHRs) were randomly divided into 2 equal group, treated with gastric perfusion of normal saline for 8 weeks. Six Wistar-Kyoto (WKY) rats were treated with normal saline as control group. Blood pressure was measured every week from the caudal vein.Eight weeks later the kidneys were taken out. Renal angiotensin Ⅱ (Ang Ⅱ ) concentration was measured by radioimmunoassay. Reverse transcriptase-polymerase chain reaction was used to detect the mRNA expression of JAK1, 2 and STAT1, 3 in the renal tissue. Western blotting was used to detect the protein expression of JAK1,2 and STAT1, 3 in the renal tissue. Results The blood pressure levels 1, 2, 4, 6,and 8 weeks after the treatment of irbesartan of the SHR- Ⅰ, group were all significandy lower than that before treatment and those of the SHR group at the corresponding days. Since 2 weeks after the treatment the blood pressure levels of the SHR- Ⅰ group were all nit significantly different from those of the WKY group (all P＞0.05 ). The degrees of glomerular hypertrophy and renal fibrosis of the SHR-Ⅰ group were significantly lower than those of the SHR group. The mRNA expression levels of Ang Ⅱ in renal cortical homogenate of the SHR-Ⅰand SHR groups were (79.4±14.8 ) pg/mg tissue and ( 83.4±8.2 ) pg/mg tissue respectively, both significantly higher than that of the WKY group (43.2±13.6) pg/mg tissue, both P＜0.01 ), and there was no significant difference in the Ang Ⅱ mRNA expression between the SHR-Ⅰ and SHR groups (P＞0.05 ). The mRNA expression levels of JAK1 and 2 and STAT1 and 3 in the renal tissues of the SHR-Ⅰ group were significantly lower than those of the SHR group (all P＜0.01 ) , and there were no significant differences between the SHR-Ⅰ group and WKY group ( all P＞0.05 ). The protein expression levels of JAK1 and 2 and STAT1 and 3 in kidneys of the SHR-Ⅰ group were significantly lower than those of the SHR group (all P＜0.01 ), and were not significantly different from those of the WKY group (all P＞0.05 ). Conclusion The JAKs-STATs pathway may be involved in the renal pathological changes in hypertension. Irbesartan attenuates the renal pathological changes by decreasing the gene expression of JAK1 and 2 and STAT1 and 3 in the renal tissues. Key words: Hypertension; Receptors angiotensin; Gene expression