To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.
Adolescence ; Adult ; Endothelin-1/urine* ; Endothelin-1/physiology ; Female ; Glomerulonephritis/urine* ; Glomerulonephritis/etiology ; Human ; Male ; Middle Age ; Nitric Oxide/urine* ; Nitric Oxide/physiology ; Nitric-Oxide Synthase/metabolism

The present study was aimed at investigating whether an altered role of nitric oxide (NO) is involved in chronic renal failure (CRF). Rats were subjected to 5/6 nephrectomy and kept for 6 weeks to induce CRF. On the experimental day, after measurement of arterial pressure under anesthesia, the arterial blood was collected, and thoracic aorta and kidney were rapidly taken. NO metabolites (NOx) were determined in the plasma, urine, aorta and kidney. The expression of NO synthase (NOS) isozymes was determined in the kidney and aorta by Western blot analysis. The expression of NOS mRNA in the glomeruli was also determined by RT-PCR. There were significant increases in arterial pressure and serum creatinine levels in CRF. Urine NOx levels were decreased in CRF, whereas plasma NOx levels were not altered. Aorta and kidney tissue NOx levels were also decreased in CRF. The expression of endothelial constitutive (ec) and inducible (i) isoforms of NOS proteins was decreased in the kidney and aorta in CRF. Accordingly, the expression of ecNOS and iNOS mRNA was decreased in the glomeruli in CRF. In conclusion, NO synthesis is decreased in the kidney and vasculature of CRF rats.
Animal ; Aorta, Thoracic/metabolism ; Comparative Study ; Enzyme Induction ; Isoenzymes/metabolism+ACo- ; Isoenzymes/genetics ; Kidney/metabolism ; Kidney Failure, Chronic/metabolism+ACo- ; Male ; Nephrectomy ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/deficiency+ACo- ; Nitric Oxide/biosynthesis ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics ; Nitrites/urine ; Nitrites/blood ; Organ Specificity ; RNA, Messenger/biosynthesis ; Rats ; Rats, Sprague-Dawley

The present study was aimed at investigating whether an altered role of nitric oxide (NO) is involved in chronic renal failure (CRF). Rats were subjected to 5/6 nephrectomy and kept for 6 weeks to induce CRF. On the experimental day, after measurement of arterial pressure under anesthesia, the arterial blood was collected, and thoracic aorta and kidney were rapidly taken. NO metabolites (NOx) were determined in the plasma, urine, aorta and kidney. The expression of NO synthase (NOS) isozymes was determined in the kidney and aorta by Western blot analysis. The expression of NOS mRNA in the glomeruli was also determined by RT-PCR. There were significant increases in arterial pressure and serum creatinine levels in CRF. Urine NOx levels were decreased in CRF, whereas plasma NOx levels were not altered. Aorta and kidney tissue NOx levels were also decreased in CRF. The expression of endothelial constitutive (ec) and inducible (i) isoforms of NOS proteins was decreased in the kidney and aorta in CRF. Accordingly, the expression of ecNOS and iNOS mRNA was decreased in the glomeruli in CRF. In conclusion, NO synthesis is decreased in the kidney and vasculature of CRF rats.
Animal ; Aorta, Thoracic/metabolism ; Comparative Study ; Enzyme Induction ; Isoenzymes/metabolism+ACo- ; Isoenzymes/genetics ; Kidney/metabolism ; Kidney Failure, Chronic/metabolism+ACo- ; Male ; Nephrectomy ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/deficiency+ACo- ; Nitric Oxide/biosynthesis ; Nitric-Oxide Synthase/metabolism+ACo- ; Nitric-Oxide Synthase/genetics ; Nitrites/urine ; Nitrites/blood ; Organ Specificity ; RNA, Messenger/biosynthesis ; Rats ; Rats, Sprague-Dawley

OBJECTIVESalt-sensitivity plays an important role in essential hypertension and is associated with more severe target organ injury and higher mortality in patients with essential hypertension. However, the pathologic mechanism of salt-sensitivity is poorly understood and endothelial dysfunction might be involved in salt-sensitive hypertension. We, therefore, observed the endothelial function changes by measuring plasma and urine nitric oxide (NO) concentrations in salt-sensitive (SS) normotensive and mild hypertensive subjects underwent various salt loading protocols and the effects of potassium supplement.

METHODSThirty-nine normotensive and mild hypertensive subjects (< 160/100 mm Hg), aged 16-60, were enrolled and the study protocol is as follows: 3 days baseline investigation, 1 week low-salt loading (3 g/day), 1 week. high-salt loading (18 g/day) and 1 week high-salt loading plus potassium chloride (4.5 g/day).

RESULTSPlasma and urine NO levels were significantly lower in SS (n = 8) subjects at baseline, low-salt and high-salt loading phases compared with salt-resistant subjects (SR, n = 31) and oral potassium supplement to SS subjects with high salt loading significantly increased plasma and urine NO levels.

CONCLUSIONEndothelial function is impaired in normotensive and mild hypertensive SS subjects. Oral potassium supplement could improve endothelial function in normotensive and mild hypertensive SS subjects.

Adult ; Antihypertensive Agents ; Blood Pressure ; Endothelium ; physiology ; Female ; Humans ; Hypertension ; epidemiology ; physiopathology ; Male ; Nitric Oxide ; blood ; urine ; Potassium, Dietary ; administration & dosage

OBJECTIVETo investigate the effects of irbesartan for heart protection and on heart nitric oxide (NO) system in diabetic rats.

METHODSThirty adult male Wistar rats were randomly divided into three equal groups, namely control group, diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the rats were sacrificed and the urine volume, body weight, ratio of heart to body weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO levels in the serum and myocardium were determined. Inducible nitric oxide synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA detected by RT-PCR.

RESULTSUrine volume, ratio of heart to body weight, plasma glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and irbesartan rats were significantly greater than those of normal controls (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and heart tissue in rats of irbesartan group were significantly decreased as compared with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression decreased significantly in irbesartan group, but not in diabetes group.

CONCLUSIONSThe abnormality in NO and iNOS mRNA expression might be related to diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein expressions and reduce NO levels in STZ-induced diabetic rats.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Biphenyl Compounds ; pharmacology ; Diabetes Mellitus, Experimental ; enzymology ; genetics ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Immunohistochemistry ; Male ; Myocardium ; enzymology ; metabolism ; Nitric Oxide ; blood ; metabolism ; urine ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazoles ; pharmacology

ObjectiveTo investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI).

METHODSSixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 μl and USCs at 1×106/200 μl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively.

RESULTSAfter 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (［81 ± 9.9］ vs ［31 ± 8.3］ and ［33 ± 4.2］ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (［11.31 ± 4.22］% vs ［6.86 ± 3.08］% and ［7.29 ± 4.84］% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (［27.31 ± 3.12］% vs ［17.38 ± 2.87］% and ［19.49 ± 4.92］%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05).

CONCLUSIONSIntracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.

Actins ; analysis ; Animals ; Arterial Pressure ; Collagen ; analysis ; Disease Models, Animal ; Erectile Dysfunction ; prevention & control ; Male ; Nitric Oxide Synthase Type I ; analysis ; Nitric Oxide Synthase Type III ; analysis ; Penile Erection ; physiology ; Penis ; innervation ; Pudendal Nerve ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; administration & dosage ; Stem Cell Transplantation ; methods ; Stem Cells ; Urine ; cytology

We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.
Acetylcholine/pharmacology ; Anemia/metabolism ; Anemia/etiology ; Anemia/drug therapy* ; Animal ; Aorta, Thoracic/physiology ; Body Weight ; Erythropoietin/pharmacology* ; Hypertension, Renal/metabolism ; Hypertension, Renal/drug therapy ; Isometric Contraction/drug effects ; Kidney/enzymology ; Kidney Failure, Chronic/metabolism* ; Kidney Failure, Chronic/complications ; Male ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/metabolism* ; Nitric-Oxide Synthase/metabolism ; Nitrites/urine ; Nitrites/blood ; Nitroprusside/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology ; Vasodilator Agents/pharmacology

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.
Aged ; Bone Density Conservation Agents/*therapeutic use ; Calcitonin/*therapeutic use ; Collagen Type II/urine ; Exercise Therapy ; Female ; Humans ; Interleukin-1beta/blood ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 3/blood ; Middle Aged ; Nitric Oxide/blood ; Osteoarthritis, Knee/*drug therapy/radiography ; Peptide Fragments/urine ; Respiratory Therapy ; Severity of Illness Index ; Treatment Outcome ; Walking

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.
Aged ; Bone Density Conservation Agents/*therapeutic use ; Calcitonin/*therapeutic use ; Collagen Type II/urine ; Exercise Therapy ; Female ; Humans ; Interleukin-1beta/blood ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 3/blood ; Middle Aged ; Nitric Oxide/blood ; Osteoarthritis, Knee/*drug therapy/radiography ; Peptide Fragments/urine ; Respiratory Therapy ; Severity of Illness Index ; Treatment Outcome ; Walking

OBJECTIVETo observe the metabolic, regulatory and anti-oxidative effects of modified Bushen Huoxue Decoction (BSHXD), a Chinese herbal medicine for kidney (Shen)-reinforcement and blood-activation, on an osteoarthritis (OA) rabbit model.

METHODSA rabbit model for knee joint OA was established by the classic Hulth's method. The OA model rabbits were randomized into 5 groups: the model control group, the positive control group treated with glucosamine sulfate, and the three BSHXD treated groups treated respectively with low, moderate, and high doses of BSHXD. In addition, a normal control group and a sham-operated group were set up. Experimental animals were sacrificed after a 7-week treatment, and pathological changes in cartilaginous tissue were estimated using the Mankin criteria. Hydroxyproline (Hyp) and malonaldehyde (MDA) contents in blood serum and urine, as well as superoxide dismutase (SOD) activity and nitric oxide (NO) content in blood serum and knee joint synovial homogenates were detected.

RESULTSMankin scoring showed insignificant statistical differences between the various treatment groups (P >0.05), but all were better than the model control group (P <0.05). Serum and urinary contents of Hyp and MDA as well as serum and synovial levels of NO were significantly lower, but the SOD activity in blood serum and synovial tissue was higher in the BSHXD treated groups than in the model group P <0.01); the effect of BSHXD was dose-dependent to some extent.

CONCLUSIONThe modified BSHXD shows an effect of improving cartilage metabolism in experimental rabbits with OA, and possesses osteo-chondric protective effects in antagonizing peroxidation injury.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Cartilage, Articular ; drug effects ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydroxyproline ; blood ; urine ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; blood ; Osteoarthritis ; blood ; drug therapy ; metabolism ; pathology ; Rabbits ; Superoxide Dismutase ; blood ; Synovial Membrane ; drug effects ; enzymology ; pathology