ABNORMAL ENDOTHELIUM-DEPENDENT RESPONSES IN EARLY RADIATION NEPHROPATHY

While arterial hypertension and renal dysfunction are well recognized complications of renal irradiation, the mechanisms that trigger the de velopment of these complications are unknown. Recently, it was reporte d that the endothelium is a major target in radiation injury. Because dysfunction of the endothelial cells may lead or contribute to the dev elopment of hypertension and renal dysfunction in radiation nephropath y, we tested the hypothesis that endothelium-dependent vasodilation is impaired in radiated kidneys prior to the onset of hypertension. To t est this hypothesis, we used Long-Evans rats that had undergone left n ephrectomy (3 weeks earlier) and irradiation (3000 r's) to the right k idney 8 days earlier (mean blood pressures in the irradiated rats were not different than in the controls). We then measured the changes in renal blood flow (RBF) induced by endothelium-dependent (acetylcholine and bradykinin) and -independent (nitroprusside, norepinephrine, and angiotensin II) vasoactive agents, We found that the increases in RBF induced by the endothelium-dependent but not independent vasodilators were markedly impaired in the irradiated kidneys. Blocking nitric oxid e synthesis with nitro L-arginine methyl ester in sham rats mimicked t he blunted responsiveness of the irradiated rats, whereas indomethacin (an inhibitor of prostaglandin synthesis) had no effect on either sha m or irradiated rats. Finally, the RBF responses to the endothelium-in dependent vasoconstrictors, norepinephrine and angiotensin II, were no t altered in the irradiated kidneys. These results suggest that renal irradiation causes endothelial dysfunction (prior to the onset of hype rtension) but spares the vascular smooth muscle cells.