ABSTRACT
Aim To determine the possibilities and mechanisms of EGFR, a receptor protein tyrosine kinase associated with many important cellular processes re-sponsible for cardiovascular remodeling in renovascular hypertensive rats. Methods 2K1C hypertensive rats were used in the present study. Blood pressure was measured with the tail-cuff method. LVMI and his-topathological changes in the cardiovascular system were analysed. EGFR expressions of aorta and myocar-dium as well as phosphorylation levels of ERK in hy-pertensive rats were detected by immunohistochemistry and Western blot analysis, respectively. Results Sys-tolic blood pressure was markedly increased 2 weeks after 2K1C surgery. Cardiovascular remodeling induced by hypertension was confirmed by elevated LVMI, pro-liferation of collagen fibers in myocardial interstitium, histopathological changes in cardiovascular system and increased IMT of thoracic aorta 6 weeks after 2 K1 C surgery. Compared with sham rats, EGFR expression in the ventricular myocardium of 2 K1 C rats was signifi-cantly increased at 6 weeks ( P<0. 05 ) , and the EG-FR/GAPDH ratio was higher in 2 K1 C rats with higher systolic blood pressure ( P < 0. 05 ) . Phosphorylation level of ERK 1/2 was upregulated correspondingly in 2 K1 C rats ( P <0. 01 ) . Increased EGFR expression was also found in aortas of 2K1C rats, particularly in tunica intima and media. Conclusion EGFR and its down-stream kinases ERK 1/2 are involved in cardio-vascular remodeling in association with the severity of hypertension in renovascular hypertensive rats.
ABSTRACT
Aim To study the effects of telmisartan upon serum calcineurin.Methods 92 male SD rats with the same age were randomly divided into control group (N), sham operation group (S), 2K1C+distilled water group (K) and 2K1C+telmisartan group (T).S rats were performed the open-abdomen surgery without being restricted any renal artery, but the K and the T rats were restricted their left renal artery. Beginning from the third week after the surgery, the K rats started to be treated with the intragastric infusion of distilled water 10 ml·(kg·d)~(-1) , while the T rats with telmisartan 10 mg·(kg·d)~(-1) .And after being treated for 2, 4 and 8 weeks, rats were respectively measured the systolic blood pressure (SBP), the diastolic blood pressure (DBP) of the abdominal aorta. Before and after the operation, ultrasonography with probe of 7.5 MHz was used to obtain the structure and functional indexes, such as IVSd, IVSs, LVPWd, and serum calcineurin were evaluated by ELISA and colorimetric assay kit.Result Compared with the S group and the N group, ① the results of blood pressure (SBP, DBP) were significantly higher in K group (all P <0.01), after use of telmisartan, blood pressure was significantly reduced(P <0.01);② the thickness of interventricular septal and left ventricular posterior wall at the end of diastolic and systolic were significantly higher in K group (all P <0.01), after use of telmisartan, the thickness of those declined(all P <0.01);③ the level and activity of serum calcineurin were significantly higher in K group (all P <0.01), after use of telmisartan, the level and activity of calcineurin significantly fell(P <0.01).Conclusion The serum calcineurin of artery was also raised in the left ventricular remodeling. Telmisartan ameliorates ventricular remodeling effectively, which may be associated with decreasing the expression of artery serum calcineurin.
ABSTRACT
The present study was aimed at examining the regulation of aquaporin (AQP)-2 water channels in the kidney in two-kidney, one clip (2K1C) hypertension. Rats were made 2K1C hypertensive for 6 weeks, and their expression of AQP2 channel proteins was determined in the clipped and contralateral kidneys. To examine the upstream affecting AQP2 channels, adenylyl cyclase activity was also determined. Along with the hypertension, in the clipped kidney, the abundance of AQP2 proteins was significantly decreased in the cortex, outer and inner medulla, while their trafficking remained unaltered. Concomitantly with the reversal of the blood pressure at 24 hours following removal of the clip, the AQP2 abundance also returned to the control level. The arginine vasopressin-evoked generation of cAMP was decreased in the clipped kidney, which again was reversed to the control level following removal of the clip. In contrast, the expression of AQP2 channels as well as the activity of adenylyl cyclase remained unaltered in the contralateral kidney. These results indicate an altered regulation of AQP2 water channels in the clipped kidney in 2K1C hypertension.