Mechanism of vasoactive peptide intermedin in vascular collagen remodeling during angiotensin II-induced hypertention.

OBJECTIVE: Renin-angiotensin axis plays a pivotal role in the cardiovascular system, and Angiotensin II (Ang II) is of great importance in the progression of hypertension. Vasoactive peptide intermedin (IMD) belongs to calcitonin gene-related peptide (CGRP) family, which is involved in the regulation of the cardiovascular function. This study aims to determine the effect of vasoactive peptide intermedin on vascular collagen remodeling caused by angiotensin II-induced hypertension. MATERIALS AND METHODS: 12-week old rats were randomly assigned into three groups, and each group consisted of 12 rats. Rats were administered with Ang II or Ang II+IMD, respectively. Control group received saline administration. Blood pressure of caudal artery was examined two weeks after administration. Serum procollagen I and III were detected by enzyme-linked immunosorbent assay (ELISA). The vascular microstructure was examined via hematoxylin-eosin (HE) staining to evaluate vascular collagen remodeling. Expressions of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) were tested by using Western-blot and RT-PCR. RESULTS: Compared with the control group (92.2±9.1 mmHg), blood pressure of group Ang II was increased by 88% (173.1±11.2 mmHg) (p<0.01). Moreover, blood pressure level in group Ang II+IMD (131.0±10.9 mmHg) was reduced compared to that in group Ang II (p<0.05). Compared with that in control group, higher level of serum procollagen, with significantly increasing vascular W/C ratio and collagen area percentage, was found in group Ang II, while all testing indexes above in group Ang II+IMD were lower than that in group Ang II. No differences were detected in the levels of Akt and MAPK mRNA among all three groups. However, highest expressions of phosphorylation Akt and MAPK protein were shown in group Ang II, and the levels were gradually lower in groups of Ang II+IMD and control. CONCLUSIONS: IMD could attenuate the vascular collagen remodeling caused by angiotensin II-induced hypertension via inhibiting phosphorylation of Akt and MAPK.

The role of protein kinase CK2 in cyclosporine-induced nephropathy in rats.

OBJECTIVES: Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin. METHODS: Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis. RESULTS: Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2. CONCLUSIONS: Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats.

Comparison of fatty acid contents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients.

OBJECTIVE: Membrane fatty acid composition plays an important role in the cellular function. Erythrocyte fatty acid composition mirrors that of myocardium and is influenced by diet. Earlier studies have shown significant alterations of membrane fatty acid composition in ethnically mixed patients with end-stage renal disease. Given the impact of ethnic and dietary factors, we sought to examine membrane fatty acid composition in an ethnically homogeneous end-stage renal disease population residing in a coastal region of Korea with high fish consumption. DESIGN: Cross-sectional study. SETTING: Outpatient facility at Dong-A University Hospital, Busan, Republic of Korea. PATIENTS: We recruited 15 stable hemodialysis patients, 14 peritoneal dialysis patients, and 10 age- and gender-matched normal controls. Patients with significant malnutrition, short duration of dialysis, recent infection, malignancy, or liver disease were excluded. Dietary intake and use of omega-3 fatty acid supplements were determined. MAIN OUTCOME MEASURE: Erythrocyte membrane fatty acid contents measured by gas chromatography. RESULTS: Palmitoleic acid and alpha-linolenic acid levels were lower, whereas oleic acid, linoleic acid, and arachidonic acid levels were higher in patients with end-stage renal disease compared with the control group. Total monounsaturated fatty acids (palmitoleic acid and oleic acid) were significantly higher in peritoneal dialysis than in hemodialysis patients. Eicosapentaenoic acid and omega-3 docosapentaenoic acid were significantly higher, but total omega-6 fatty acids, omega-6/omega-3, and arachidonic acid/eicosapentaenoic acid ratios were significantly lower in hemodialysis patients consuming omega-3 supplements compared with those who did not. CONCLUSION: Patients with end-stage renal disease exhibited significant alterations in erythrocyte membrane fatty acids, which were partially modified by the dialysis modality and omega-3 fatty acid supplementation.