title: The role of nitric oxide in radiation nephropathy.
abstract: Sufficient radiation will cause kidney injury with hypertension, azotemia, and death from renal failure. There is early endothelial injury after radiation, which could lead to a deficit of constitutive nitric oxide (NO) synthesis, with capillary thrombosis and hypertension, both of which are seen in radiation nephropathy. In a rat radiation nephropathy model, the serial evolution of urinary cyclic guanosine monophosphate (cGMP), a marker of kidney NO, was studied and a deficit in urinary cGMP was found. This radiation-induced cGMP deficit was prevented by high-dose Captopril treatment. Low-dose Captopril treatment protected against radiation nephropathy without preventing the decrease in urinary cGMP. An inhibitor of NO synthesis, L-N-arginine-methylester, did not blunt the beneficial effect of Captopril treatment. We conclude that there is a deficit in urinary cGMP in radiation nephropathy, but that prevention of this deficit is not essential in the prevention of radiation nephropathy by Captopril.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Cohen
authors.forename: B L
authors.initials: BL
authors.lastname: Fish
authors.forename: J E
authors.initials: JE
authors.lastname: Moulder
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002216:Captopril / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000652:urine; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010865:Pilot Projects; D011833:Radiation Injuries, Experimental; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014185:Transplantation, Isogeneic; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; D009569:Nitric Oxide; D002216:Captopril; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester