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

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