The role of nitric oxide in radiation nephropathy.
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.
Cohen
E P
EP
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Fish
B L
BL
Moulder
J E
JE
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*
D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; D009569:Nitric Oxide; D002216:Captopril; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester