Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.
Animal ; Anticoagulants/pharmacology* ; Cell Movement/drug effects ; Female ; Heparin/pharmacology* ; Ischemia/pathology* ; Kidney/pathology ; Kidney/drug effects* ; Neutrophils/physiology ; Neutrophils/drug effects* ; Renal Circulation* ; Reperfusion Injury/pathology* ; Sheep

BACKGROUNDMedical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin II (AII), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis.

METHODSEighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases) and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml (35 µg/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, AII, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared.

RESULTSTwenty days after the treatment, in ozone therapy group, PRA was (1.31 ± 0.12) ng·ml⁻¹·h⁻¹, AII (111.25 ± 17.35) pg/ml, ALD (251.31 ± 22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23 ± 0.13) ng·ml⁻¹·h⁻¹, AII (155.18 ± 19.13) pg/ml, ALD (405.31 ± 29.88) pg/ml, t = 4.67 - 14.23, P < 0.01), also lower than those of control group 20 days after the treatment (PRA (2.02 ± 0.11) ng·ml⁻¹·h⁻¹, AII (162.21 ± 15.32) pg/ml, ALD (401.20 ± 35.02) pg/ml, t = 4.97 - 15.61, P < 0.01); renal blood flow was (175.15 ± 28.20) ml/min, which increased compared with that before the treatment ((125.68 ± 21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59 ± 23.15) ml/min, t = 4.78, 4.61, P < 0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (χ² = 5.295, P < 0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (χ² = 12.993, P < 0.01).

CONCLUSIONSBasic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, AII and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients.

Adult ; Female ; Hepatitis, Chronic ; drug therapy ; Humans ; Kidney ; blood supply ; drug effects ; metabolism ; Male ; Middle Aged ; Ozone ; therapeutic use ; Renal Circulation ; drug effects

OBJECTIVE: To observe the changes of vasoactive substances in rabbits administered with mannitol at different dosages and to investigate the mechanism of acute renal failure (ARF) induced by massive mannitol administration. METHODS: Eighteen healthy male New Zealand rabbits were randomly divided into 3 groups: a minor mannitol group (n=6, mannitol 8 g/kg within 2 hours), a control group (n=6, saline of the same volume), and a massive mannitol group with free water taking (n=6, mannitol 40~60 g/kg within 3 days). The changes of renin, angiotensin-I (ang-I), angiotensin-II (ang-II), endothelin (ET), and atrial natriuretic factor(ANF) in the serum were observed. RESULTS: No significant changes in the renin, ang-I, ang-II, ET, and ANF in the serum were found between the minor mannitol group and the saline control group (P> 0.05). In the massive mannitol group with free water taking, renin, ang-I, and ang-II in the serum increased significantly compared with the other 2 groups; ET in the serum decreased significantly compared with the saline control group (P< 0.05); no significant changes in the ANF in the serum were found compared with the other 2 groups(P> 0.05). CONCLUSION ARF induced by massive mannitol administration is associated with a significant change of vasoactive substances.
Acute Kidney Injury ; blood ; chemically induced ; physiopathology ; Angiotensins ; blood ; Animals ; Atrial Natriuretic Factor ; blood ; Dose-Response Relationship, Drug ; Endothelins ; blood ; Male ; Mannitol ; administration & dosage ; toxicity ; Rabbits ; Random Allocation ; Renal Circulation ; drug effects ; Renin-Angiotensin System ; drug effects

OBJECTIVETo investigate the effect of traditional classical compound Wulingsan on renal hemodynamic in rats with adriamycin (ADR)-induced nephrosis.

METHODAfter establishing a model of rats with adriamycin-induced nephrosis, we administrated wulin-san to the ADR rats via oral gavage for four weeks and measured mean arterial blood preasure (MABP) with manometer. Renal clearance of paraaminohippuric acid (PAH) and inulin were detected, then renal plasma flow (RPF) and glomerular filtration rate (GFR) were calculated. Renal vascular resistance (RVR) was calculated as the division of MABP by RPF. Renal endothelin (ET) and angiotensin II (Ang II) were detected with radioimmunity assay kits, and nitrous oxide (NO) was detected with biochemical kits.

RESULTThere was no significant change of GFR in ARD rats, but RPF and NO were decreased, which accompanied by enhanced RVR, ET and Ang II. RPF was increased in the administrated rats, in company with RVR, ET and Ang II decreased, whereas NO was not influenced after the administration.

CONCLUSIONWulingsan can improve the renal hemodynamic in ADR rats, at least in part by modulating the levels of vasoactive factor.

Angiotensin II ; metabolism ; Animals ; Doxorubicin ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelins ; metabolism ; Glomerular Filtration Rate ; drug effects ; Kidney ; metabolism ; physiopathology ; Male ; Medicine, Chinese Traditional ; Nephrosis ; chemically induced ; metabolism ; physiopathology ; Nitrous Oxide ; metabolism ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Renal Circulation ; drug effects ; Renal Plasma Flow ; drug effects ; Vascular Resistance ; drug effects

OBJECTIVETo investigate the changes and the effects of captopril on the renal blood flow and microvascular perfusion in dogs with acute cardiac insufficiency.

METHODSAcute cardial insufficiency was induced by combining occlusion of the left anterior descending artery with right ventricular pacing in 12 mongrel dogs. The ascending aorta and left kidney were dissected and ultrasonic flow probes were placed on ascending aorta and renal artery to monitor cardiac output (CO) and renal blood flow (RBF). Contrast-enhanced ultrasound of the kidney was performed as CO was reduced to 25% (LCO25%) and 50% (LCO50%) from the basic measurement and microvascular flow velocity (beta), microvascular volume (A) and microvascular blood flow (renal cortex) were observed. After CO reduced to 50%, captopril 1 mg/kg and 2 mg/kg were injected successively and contrast-enhanced ultrasound of the kidney were performed again before and after injection.

RESULTSAt baseline, CO, RBF, CXbeta (beta of renal cortex), A and A x beta were (1.46 +/- 0.16) ml/min, (107.5 +/- 35.7) ml/min, 1.39 +/- 0.14, 120.3 +/- 14.8 and 167.4 +/- 25.0, respectively. After the LCO25% was reached, RAF, CXbeta, A and A x beta decreased to (72.50 +/- 32.4) ml/min, 0.87 +/- 0.082, 117.6 +/- 13.1, and 102.6 +/- 15.5, respectively. The corresponding values after the LCO50% was reached were (44.1 +/- 17.2) ml/min, 0.61 +/- 0.039, 106.9 +/- 12.0, and 64.7 +/- 8.83, respectively. It is suggested that the volume of the renal microvasculature remained stable until the LCO50% was reached. When captopril 1 mg/kg and 2 mg/kg were injected successively at LCO50%, MAP decreased from (85.4 +/- 7.8) mm Hg to (78.7 +/- 7.3) mm Hg and to (69.1 +/- 6.3) mm Hg (P < 0.05), respectively, while CO increased from 0.73 +/- 0.084 to 0.83 +/- 0.065 and to 0.9 +/- 0.054 (P < 0.05), respectively. RBF increased from (44.1 +/- 17.2) ml/min to 60.3 +/- 17.8 and to 79.4 +/- 17.8 (P < 0.05), respectively. After captopril 1 mg/kg and 2 mg/kg were injected, the increased flow ratios with CO were 0.15 +/- 0.084 and 0.31 +/- 0.011, respectively, and with RBF were 0.29 +/- 089 and 0.522 +/- 0.040, respectively. The increased renal blood flow ratio was higher than that of CO after captopril was used. The corresponding increases were from 0.61 +/- 0.039 to 0.75 +/- 0.020 and to 0.86 +/- 0.027 for CX beta, from 106.9 +/- 11.9 to 115.4 +/- 11.1 and to 116.6 +/- 8.9 for A, from 64.7 +/- 8.83 to 87.0 +/- 8.6 and to 100.6 +/- 8.9 for A x beta, respectively.

CONCLUSIONThe renal microvasculature plays a role by keeping its volume stable in the protection against renal ischemia when acute cardiac output decreases slightly. The role of captopril to improve renal microvascular perfusion is independent of increased total cardiac output or increased systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Captopril ; pharmacology ; therapeutic use ; Cardiac Output, Low ; complications ; drug therapy ; physiopathology ; Dogs ; Female ; Kidney ; blood supply ; diagnostic imaging ; Male ; Perfusion ; Renal Circulation ; drug effects ; Ultrasonography

Intravascular administration of magnesium (Mg) causes vasodilation and increases renal blood flow. The aim of this study was to investigate the renal effect of Mg following unclamping of the supraceliac aorta. Mongrels were divided into two groups, control (group C, n=7) and Mg group (group Mg, n=7). In group Mg, 30 mg/kg MgSO4 was injected as a bolus immediately prior to unclamping the supraceliac aorta and thereafter as an infusion (10 mg/kg/hr). The group C received an equivalent volume of saline solution. Systemic hemodynamics, renal artery blood flow, renal cortical blood flow (RCBF), renal vascular resistance, and renal function were compared. Following the aortic unclamping, cardiac output and RCBF were less attenuated, and the systemic and renal vascular resistance was elevated to a lesser degree in the group Mg compared to the group C. There was no significant difference in the plasma renin activity, serum creatinine and Cystatin-C between the two groups. The present study shows that Mg infusion improves systemic hemodynamics and RCBF after aortic unclamping. However, we did not observe any improvement in renal function when Mg was administered after supraceliac aortic unclamping.
Animals ; Aorta, Abdominal/physiology/*surgery ; Blood Pressure/drug effects ; Calcium/blood ; Cardiac Output/drug effects ; Comparative Study ; Creatinine/blood ; Cystatins/blood ; Dogs ; Female ; Heart Rate/drug effects ; Magnesium/blood ; Magnesium Sulfate/*pharmacology ; Male ; Renal Circulation/*drug effects ; Renin/blood ; Research Support, Non-U.S. Gov't

OBJECTIVES: Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. METHODS: To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. RESULTS: Diabetic rats exhibited significantly elevated plasma and urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. CONCLUSIONS: NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest that excessive NO production may contribute to renal hyperfiltration and hyperperfusion in early diabetes.
Animal ; Diabetes Mellitus, Experimental/physiopathology ; Diabetes Mellitus, Experimental/complications ; Diabetic Nephropathies/physiopathology ; Diabetic Nephropathies/etiology* ; Enzyme Inhibitors/pharmacology ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/biosynthesis* ; Nitric-Oxide Synthase/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Renal Circulation/drug effects ; Support, Non-U.S. Gov't

OBJECTIVETo explore influence of sodium restricted diet and non-sodium restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood flow (RBF) and subside of ascites in patients with cirrhotic ascites.

METHODSEighty cases of hepatitis B with cirrhotic ascites were randomly divided into sodium restricted diet group and non-sodium restricted diet group. 39 cases were in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily; 41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg daily. Both groups received diuretics furosemide and spironolactone. Blood sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after treatment.

RESULTSIn non-sodium restricted diet group, blood sodium and urine sodium increased 10 days after treatment compared with those before treatment, and compared with those of sodium restricted diet group 10 days after treatment, P <0. 01. RBF increased compared with that before treatment, and compared with that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal damage induced by low blood sodium after treatment was less in non-sodium restricted diet group than that in sodium restricted diet group, P <0. 05. Ascites disappearance upon discharge was more in sodium restricted diet group than that in non-sodium restricted diet group, P <0. 01. Time of ascites disappearance was shorter in non-sodium restricted diet group than that in sodium restricted diet group, P < 0. 01.

CONCLUSIONCompared with sodium restricted diet, while using diuretics of both groups, non-sodium restricted diet can increase level of blood sodium, thus increasing excretion of urine sodium and diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal blood flow and prevent renal damage induced by low blood sodium and facilitate subsiding of ascites.

Ascites ; blood ; diet therapy ; physiopathology ; urine ; Chymosin ; blood ; Diet, Sodium-Restricted ; methods ; Diuretics ; administration & dosage ; Female ; Furosemide ; administration & dosage ; Hepatitis B ; blood ; diet therapy ; physiopathology ; urine ; Humans ; Liver Cirrhosis ; blood ; diet therapy ; physiopathology ; urine ; Male ; Middle Aged ; Renal Circulation ; drug effects ; Sodium ; blood ; urine ; Sodium, Dietary ; administration & dosage ; Spironolactone ; administration & dosage

OBJECTIVETo explore the effects of dialysate contained Chinese herbs for replenishing qi and activating blood circulation on platelet membranous glycoprotein CD62P in patients with chronic renal failure (CRF) undergoing hemodialysis.

METHODSForty patients underwent maintaining hemodialysis were randomly assigned to two groups, the Western medicated group (WMG) and the Chinese herbs group (CHG). The content of CD62P in all patients was detected by ELISA before and after hemodialysis.

RESULTSThe levels of blood urea nitrogen, creatinine, potassium, hematocrit, platelet count and carbon dioxide combining power (CO2CP) as well as the expression of CD62P after treatment were significantly changed in both groups with significant difference as compared with those before treatment (both P < 0.05). And comparison between the two groups in expression of CD62P after treatment also showed significant difference (P < 0.05). But the improvement in TCM syndrome between the two groups was insignificantly different (P > 0.05).

CONCLUSIONHemodialysis with dialysate containing Chinese herbs of replenishing qi and activating blood circulation can decrease the expression of platelet membranous glycoprotein CD62P, which may be associated with the mechanism of Chinese herbs in treating CRF.

Adult ; Blood Circulation ; Blood Platelets ; drug effects ; metabolism ; Combined Modality Therapy ; Dialysis Solutions ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Kidney Failure, Chronic ; blood ; therapy ; Male ; Middle Aged ; P-Selectin ; blood ; Phytotherapy ; Qi ; Renal Dialysis ; methods