Lipid peroxidation and renal injury in renal ischemic reperfusion: effect ofangiotensin inhibition.

OBJECTIVES: To investigate the role of angiotensin inhibition on lipid peroxidation (LPO) and renal pathology in ischemic reperfusion (IR). MATERIAL AND METHOD: Male Wistar rats were subjected to 15-, 30-, 45- or 60- minutes ofrenal ischemia (I) by left renal artery occlusion. In the 30-minute I group, reperfusion (R) for I day (13,R) was performed in additional animals that had been treated with water, angiotensin converting enzyme inhibitor (ACE]; enalapril 5 mg/kg/d), or angiotensin receptor type 1 blocker (ARB; losartan 10 mg/kg/d) one day before I and were continued for 1 day after R. Renal tissue malondialdehyde (MDA), an indicator of LPO, was examined during I and IR periods. Renal pathology was also determined. RESULTS: During ischemia, renal tissue MDA levels were increased throughout the 60-minute ischemic period and was maximum at 30 minutes of ischemia (p < 0.01). Histological changes in 30-minutes I group showed slight tubular cell congestion and mild interstitial edema. One day after reperfusion, MDA levels were still elevated (p < 0. 01) when compared with sham. Progression of renal pathology was observed after I day of reperfusion. Both ACEI and ARB could attenuate the heightened MDA levels (p < 0.01). IR-induced renal injury was markedly diminished by administration ofACEI as well as by ARB. CONCLUSION: These results indicate that inhibition of angiotensin could reduce lipid peroxidation and ameliorate renal injury during IR condition.

Citrate attenuates tubulointerstitial fibrosis in 5/6 nephrectomized rats by decreasing transforming growth factor-beta1.

OBJECTIVE: Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human. MATERIAL AND METHOD: Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation. RESULTS: Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005). CONCLUSION: As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.

Acute hypercalcemia-induced hypertension: the roles of calcium channel and alpha-1 adrenergic receptor.

OBJECTIVE: To study the mechanism(s) of acute hypercalcemia-induced hypertension in dogs. MATERIAL AND METHOD: Adult male mongrel dogs were intravenously infused with: 1) normal saline solution, 2) CaCl2 solution, 3) CaCl2 + calcium channel blocker (verapamil), 4) CaCl2 + selective alpha-1 adrenergic receptor blocker (prazosin), or 5) CaCl2 + verapamil + prazosin. Either verapamil or prazosin treatment was started at forty minutes before CaCl2 infusion and then was co-administered throughout the three-hour experimental period. Systemic and renal hemodynamics parameters were determined. RESULTS: Infusion of CaCl2 caused increases in mean arterial blood pressure (p < 0.01), total peripheral resistance (p < 0.001), and renal vascular resistance (p < 0.001). Prior treatment with either verapamil or prazosin lowered baseline blood pressure (p < 0.01) and could prevent hypercalcemia-induced hypertension. This occurred accompanying regaining to near normal values of abnormal systemic hemodynamics parameters. Combination of both drugs showed more profound effects, particularly on lowering renal vascular resistance. CONCLUSION: Acute hypercalemic hypertension is caused by an increase in vascular resistance mediated via the direct effect of calcium on vascular smooth muscle as well as the indirect effect of calcium induced hypercatecholaminemia. The stimulatory effect of hypercalcemia on renal vascular resistance is more prominent than that on peripheral vascular resistance.