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.
Blotting, Western ; Desoxycorticosterone ; Heat-Shock Proteins* ; Hot Temperature* ; Humans ; Hypertension* ; Kidney* ; Male ; Rats, Sprague-Dawley ; Up-Regulation*

Whether there exists a sympathetic neural regulation on the aquaporin (AQP) channels in the kidney was examined. Male Sprague-Dawley rats were used. They were renal nerve denervated by stripping the nervous and connective tissues passing along the renal artery and vein, and painting these vessels with 10% phenol solution through a midline abdominal incision. Three days later, the expression of AQP1-4 proteins in the denervated kidneys was determined. The content of norepinephrine was found significantly decreased following the denervation. Accordingly, the expression of AQP2 proteins was markedly decreased. The expression of AQP3 and AQP4 was also slightly but significantly decreased, while that of AQP1 was not. Neither the basal nor the AVP-stimulated accumulation of cAMP was significantly affected in the denervated kidney. It is suggested that the sympathetic nervous system has a tonic stimulatory effect on AQP channels in the kidney.
Animals ; Aquaporin 2 ; Aquaporins* ; Connective Tissue ; Denervation ; Humans ; Kidney* ; Male ; Norepinephrine ; Paint ; Paintings ; Phenol ; Rats* ; Rats, Sprague-Dawley ; Renal Artery ; Sympathetic Nervous System ; Veins

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.
Animals ; Basilar Artery ; Blood Pressure ; Calcium Channels ; Calcium* ; Desoxycorticosterone ; Desoxycorticosterone Acetate ; Hypertension ; Hypertension, Renal* ; Microscopy ; Muscle, Smooth, Vascular* ; Rats ; Rats, Sprague-Dawley ; Renal Artery

The present study was conducted to investigate the possible role of the sympathetic nervous system in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension. 2K1C and DOCA-salt hypertension were made in Sprague-Dawley rats. Four weeks after induction of hypertension, systolic blood pressure measured in conscious state was significantly higher in 2K1C (216+/-18 mmHg) and DOCA-salt (205+/-29 mmHg) groups than that in control (128+/-4 mmHg). The third branches (<300 micrometer in outer diameter) of the mesenteric artery were isolated and cut into ring segments of 2apprx3 mm in length. Each ring segment was mounted in tissue bath and connected to a force displacement transducer for measurement of isometric tension. The arterial rings were contracted by application of norepinephrine (NE) in a dose-dependent manner. The amplitude of the NE-induced contraction of the vessels was significantly larger in hypertension than in control. The NE-induced contraction was significantly enhanced by neuropeptide Y (NPY) in hypertension. Reciprocally, NPY-elicited vasocontraction was increased by NE in hypertension. These results suggest that the sympathetic nervous system contributes to the development of 2K1C and DOCA-salt hypertension.
Animals ; Baths ; Blood Pressure ; Desoxycorticosterone ; Hypertension ; Mesenteric Arteries* ; Neuropeptide Y* ; Neuropeptides* ; Norepinephrine* ; Rats* ; Rats, Sprague-Dawley ; Sympathetic Nervous System ; Transducers

Resveratrol (RSV) may provide numerous protective eff ects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the eff ects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, p47(phox), Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced NF-κB activation by promoting IκB-α degradation. Meanwhile, the observed increases in nuclear NF-κB, NOX4, p47(phox), and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting NF-κB activation.
Acetylcysteine ; Animals ; Anoxia ; Bays ; JNK Mitogen-Activated Protein Kinases ; Lipid Peroxidation ; Mice* ; Oxidative Stress* ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Reactive Oxygen Species ; Sirtuin 1

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.
Animals ; Blotting, Western ; Desoxycorticosterone ; Hypertension ; Kidney ; Nitric Oxide* ; Nitrites ; Protein Isoforms ; Rats*

Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome).
Acetylcholine ; Animals ; Aquaporin 2 ; Atherosclerosis ; Blood Pressure ; Cardio-Renal Syndrome ; Diabetes Insipidus, Nephrogenic ; Fibrosis ; Heart Failure ; Humans ; Hypertension ; Hypertrophy, Left Ventricular ; Kidney ; Mice ; Myocardial Infarction ; Myocardium ; Neurons ; Nitric Oxide ; Rats ; Relaxation ; Renal Insufficiency, Chronic ; Risk Factors ; Tissue Donors ; Ureteral Obstruction

Purpose: Congenital heart disease (CHD) is a known risk factor for acquired cardiovascular and cerebrovascular diseases. However, available evidence on CHD is limited mostly to Western populations. This study aimed to evaluate the prevalence of vascular events and all-cause mortality in Korean patients with CHD and to further corroborate CHD as a predictor of vascular events and all-cause mortality. Materials and Methods: The claims data of the Korean National Health Insurance Service (NHIS) were retrospectively reviewed. Information regarding diagnostic codes, comorbidities, medical services, income level, and residential area was also collected. Outcomes of interest included stroke, myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE). Results: We included 232203 patients with CHD and 3024633 individuals without CHD as a control group through age- and sexmatched 1:10 random sampling. The prevalences of hypertension, congestive heart failure, ischemic heart disease, hyperlipidemia, and atrial fibrillation were significantly higher in the CHD group, which had a more than two-fold higher incidence of vascular events and all-cause mortality, than in the group without CHD. Multivariable models demonstrated that CHD was a significant risk factor for stroke, MI, all-cause mortality, and MACE. Conclusion In conclusion, this nationwide study demonstrates that Korean patients with CHD have a high incidence of comorbidities, vascular events, and mortality. CHD has been established as an important predictor of cardiovascular events. Further studies are warranted to identify high-risk patients with CHD and related factors to prevent vascular events.

BACKGOUND: The present study examined whether a blockade of nitric oxide (NO) synthesis affects the regulation of aquaporin (AQP) water channels in rats subjected to renal ischemia/reperfusion (I/R). METHODS: Renal I/R was experimentally induced by clamping the left renal artery for 60 minutes in rats. The rats were kept for 7 days thereafter, during which they were supplied with tap water containing NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/L). The expression of AQP1-3 was determined in the kidney by Western blot analysis. RESULTS: In renal I/R injury, the expression of AQP2 was significantly decreased. The treatment with L-NAME further diminished the expression of AQP2. Although the expression of either AQP1 or AQP3 was not significantly altered in the kidney subjected to I/R, it was also significantly decreased by the treatment with L-NAME. CONCLUSION: It is suggested that endogenous NO system should play a role in the regulation of AQP water channels in rat kidney subjected to I/R injury.
Animals ; Aquaporins* ; Blotting, Western ; Constriction ; Ischemia ; Kidney* ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Rats* ; Renal Artery ; Reperfusion

Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3beta was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% +/- 5.3% in the sauchinone group vs 44.4% +/- 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3beta was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.
Animals ; Benzopyrans/*pharmacology ; Dioxoles/*pharmacology ; Glycogen Synthase Kinase 3/metabolism ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Myocardial Reperfusion Injury/*metabolism/pathology/prevention & control ; Phosphorylation ; Protective Agents/*pharmacology ; Rats ; Signal Transduction/*drug effects ; p38 Mitogen-Activated Protein Kinases/*metabolism