Effects of aerobic exercise time on cardiovascular and renal functions of 2K1C renal vascular hypertensive rats / 中国病理生理杂志

AIM: To explore the impact of aerobic exercise (AE) time on mean arterial pressure (MAP), sinus bradycardia, heart and kidney histological changes and oxidative damage in the two-kidney and one-clip (2K1C) hypertensive rats, and to assess the specific effects of AE time on alleviation of hypertension.METHODS: Healthy male Wistar rats (n=60) were randomly divided into sham operation (sham) group and 2K1C group.After operation, the rats in these 2 groups were divided into sham sedentary (sham+SED) group, sham exercise (sham+AE) group, 2K1C se-dentary (2K1C+SED) group and 2K1C exercise (2K1C+AE) group.The rats in sham+AE group and 2K1C+AE group were subjected to AE for 10 weeks: swimming for 1 h/d.The MAP, sinus bradycardia and the histological changes of heart and kidney in these 4 groups were tested regularly.RESULTS: Compared with 2K1C+SED group, the rats in 2K1C+AE group had significantly improved MAP and sinus bradycardia at the 4th week, with reduced collagen deposition in the myocardium and kidney, decreased level of thiobarbituric acid reactive substances (TBARS) in the left ventricle and increased catalase (CAT) activity in the left ventricle and kidney.The results of the 6th to 10th weeks showed that the differences of MAP and sinus bradycardia between the rats in 2K1C+AE group and 2K1C+SED group had gradually narrowed.The TBARS levels in the left ventricle and kidney and CAT activity in both kidneys of the rats in 2K1C+AE group were partly restored at the 8th week.The collagen deposition in the heart and kidney of the rats in AE group was reduced to the lowest level at the 10th week.CONCLUSION: Short-time (about 4 weeks) AE effectively improves the MAP and sinus bradycardia of 2K1C renal vascular hypertensive rats and attenuates the damages of the heart and kidney by regulating oxidative stress, thus improving the cardiovascular and renal functions of 2K1C renal hypertensive rats.

Epidermal growth factor receptor involvement in cardiovascular remodeling in renovascular hypertensive rats / 中国药理学通报

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.

Influence of Telmisartan on peripheral calcineurin of rat with two kidneys one clip hypertension / 中国药理学通报

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.

Effects of?1 adrenoceptor antisense on blood pressure and?1 adrenoceptor mRNA and protein in renal hypertension rats / 中华急诊医学杂志

Objective To evaluate the effects of 131 adrenoceptor anfisense on blood pressure and?1 adrenoceptor mRNA and protein levels in 2 kidney 1 clip(2K1C)rats.Method 2KIC hypertensive rots were produced by clipping renal artery of SD rats.Liposome/AS-ODNs 2.0 were tested intravenously in rats with 2KIC hypertension.Animals were divided into 5 groups(n=18 in each group):?1-AS-ODN group,?1-IN-ODN group,2K1C group,Sham group and SD group.Blood pressure was measured by tail-cuff method,the levels of myocardial?adreneceptor mRNA and protein were tested by RT-PCR and binding assay.Results On the basis of the magnitude and duration of hypotension,?1-AS-ODN decreased blood pressure by 39 mmHg at the most for 4 weeks.Compared with the 2KIC group,?1-AS-ODN did not significantly change the levels of myocardial?1 adrenoceptor mRNA but significantly decreased the levels of myocardial?1 adrenoceptor protein at 2,7,30 days (P

Upregulation of Heat Shock Proteins in the Kidney in Hypertension

The present study was undertaken to determine the regulation of heat shock proteins (HSP) in the kidney in hypertension. Two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA) -salt hypertension was induced in male Sprague-Dawley rats. At weeks 1 and 4 after inducing the hypertension, the expression of HSP70, HSP32 and HSP25 was determined in the kidney by Western blot analysis. In 2K1C hypertension, the expression of HSP70, HSP32 and HSP25 was increased in the clipped kidney at both weeks 1 and 4. However, in the contralateral kidney, their expression was not significantly altered at week 1, but increased at week 4. In DOCA-salt hypertension, the expression of HSP remained unaltered in the remnant kidney at week 1, but significantly increased at week 4. These results indicate that HSP are differentially regulated in the kidney according to the duration and the model of hypertension.

Differential Regulation of Atrial Natriuretic Peptide in Clipped and Contralateral Kidneys in Two-Kidney, One Clip Hypertension / 대한신장학회잡지

BACKGROUND: The present study was aimed to determine the pathophysiological implications of local atrial natriuretic peptide (ANP) system in the kidney in two- kidney, one clip (2K1C) hypertension. METHODS: Rats were made 2K1C hypertensive, and their mRNA expressions of ANP and natriuretic peptide receptors (NPR) were determined in the clipped and contralateral kidneys by reverse transcription-polymerase chain reaction. RESULTS: The expression of ANP was decreased in the clipped kidney and increased in the contralateral kidney. Similarly, the expression of both NPR-A and NPR-C was decreased in the clipped kidney and increased in the contralateral kidney. CONCLUSION: These findings indicate a differentially-altered ANP system in the clipped and the contralateral kidneys in 2K1C hypertension.

Altered Renal Expression of Aquaporin-2 Water Channels in Rats with Experimental Two-Kidney, One Clip Hypertension

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.

Altered Resting Nitric Oxide Vasodilator Tone in Two-Kidney, One Clip Rats / 대한신장학회잡지

Endogenous nitric oxide(NO) plays an important role in the regulation of blood pressure. It has been known that the evoked NO-dependent dilator system may be impaired in various hypertensive models. The effects of NG-nitro-L-arginine(L-NNA), lipopolysaccharide(LPS) and tempol on mean arterial pressure(MAP) and the effects of L-NNA on isolated aorta tone were studied in order to elucidate potential alterations in resting vasodilator tone of NO in two-kidney, one clip(2K1C) hypertension. Plasma nitrite/nitrate levels were measured by colorimetric assay, and the expression of endothelial and inducible NO synthases(eNOS, iNOS) was determined by Western blot analysis. L-NNA caused an increase of MAP, while LPS produced a hypotensive effect in both 2K1C and control rats. The magnitude of the pressor or depressor response to L-NNA and LPS was comparable in the two groups. Tempol induced a sustained decrease in MAP in 2K1C rats, while it had no effects on MAP in control rats. Plasma concentrations of NO metabolites were significantly increased following the LPS-treatment in both 2K1C and control rats, while they were not affected by tempol-treatment. In endothelium-intact aortic rings precontracted with 25 mM KCl, L-NNA caused a dose-dependent contraction. The magnitude of the maximal contraction was attenuated in 2K1C rats as compared with control. An inhibition of contractile responses to L-NNA in the hypertensive group was also shown in rubbed rings, although the magnitude of contractions was markedly reduced. The vascular expression of both eNOS and iNOS was significantly decreased in 2K1C rats as compared with control. These results indicate that 2K1C hypertension is associated with a reduced basal vasodilator tone of NO and a decrease in the vascular expression of NOS isozymes.

Increased expression of nitric oxide synthase coincides with reversal of renovascular hypertension

The present study was aimed at investigating whether there are changes in the expression of nitric oxide synthase (NOS) in relation with the unclipping-induced fall of blood pressure in two-kidney, one clip (2K1C) hypertension. Male Sprague-Dawley rats were made 2K1C hypertensive by clipping the left renal artery for four weeks. Sham-clipped rats served as control. The expression of endothelial constitutive (ec) NOS proteins and tissue levels of NO metabolites were determined in the kidney. Systolic blood pressure was significantly increased in clipped rats compared with that in the control. The development of hypertension was associated with decreases in the expression of ecNOS proteins and tissue levels of NO metabolites in the clipped kidney. The blood pressure at twenty-four hours after removal of the renal arterial clip fell to the control level. Accordingly, in the unclipped kidney, the expression of ecNOS proteins and tissue contents of NO metabolites were increased to the control level. The contralateral kidney was not affected by the development or reversal of hypertension. It is suggested that an enhanced expression of ecNOS in the unclipped kidney is an important component in the reversal of renovascular hypertension.

Tissue-Specific Regulation of Angiotensinogen and Angiotensin II Receptor Genes in Two-Kidney, One Clip Hypertensive Rats / 대한신장학회잡지

The present study was aimed at investigating the molecular regulation of the renin- angiotensin system (RAS) in two-kidney, one clip (2K1C) hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes was determined by Northern blot analysis in rats made 2K1C hypertensive for 2 or 4 weeks. The expression of renin gene was increased in the clipped kidney and decreased in the contralateral non-clipped kidney at weeks 2 and 4. The expression of angiotensinogen gene was not significantly altered at week 2, but increased at week 4 in the clipped kidney. However, it was not significantly altered in the contralateral kidney either at week 2 or 4. Nor was the expression of angiotensinogen gene significantly altered in the liver either at week 2 or 4. On the other hand, the expression of angiotensin II receptor gene was decreased at week 2, and increased at week 4 in the clipped kidney, whereas it was not significantly changed in the contralateral kidney either at week 2 or 4. In the liver, the expression of angiotensin II receptor gene was not significantly altered at week 2, but decreased at week 4. These results suggest that the components of RAS are transcriptionally regulated in 2K1C hypertension in a manner dependent on tissues and duration of hypertension.

Altered Calcium Current of the Vascular Smooth Muscle in Renal Hypertension

The present study was aimed at investigating whether the calcium current in the vascular smooth muscle (VSM) cells is altered in renal hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in Sprague-Dawley rats. Rats without clipping the renal artery or implanting DOCA were used as control for 2K1C and DOCA-salt hypertension, respectively. Four weeks after clipping, systolic blood pressure was significantly higher in 2K1C rats than in control (192+/-24 and 119+/-4 mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure (180+/-15 mmHg, n=18) compared with control (121+/-6 mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured 5 ~ 10 mum in width and 70 ~ 150 mum in length were obtained. VSM cells could not be differentiated in size and shape between hypertensive and normotensive rats under light microscopy. High-threshold (L-type) calciumcurrents were recorded using whole-cell patch clamp technique. The amplitude of the current recorded from VSM cells was larger in 2K1C hypertension than in control. Neither the voltage-dependence of the calcium current nor the cell capacitance was significantly affected by 2K1C hypertension. By contrast, the amplitude of the calcium current was not altered in DOCA-salt hypertension. These results suggest that high-threshold calcium current of the VSM cells is altered in 2K1C hypertension, and that calcium channel may not be involved in calcium recruitment of VSM in DOCA-salt hypertension.

Altered renal nitric oxide system in experimental hypertensive rats

The present study was aimed at investigating whether the development of hypertension is related with an altered expression of nitric oxide synthases (NOS) in the kidney. By Western blot analysis, the expression of bNOS and ecNOS isoforms was determined in the kidney of deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2K1C) rats. In DOCA-salt hypertension, the expression of both bNOS and ecNOS was decreased, along with tissue contents of nitrites. In 2K1C hypertension, the nitrite content of the clipped kidney was decreased along with ecNOS levels, whereas neither the nitrite content nor the expression of NOS isoforms was significantly altered in the contralateral non-clipped kidney. These results suggest that the development of hypertension is associated with an altered renal expression of NOS and nitric oxide generation in DOCA-salt and 2K1C rats.