Abnormal endothelium-dependent responses in early radiation nephropathy

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Radiation Oncology

Background:

• Arterial hypertension and renal dysfunction are known complications of renal irradiation.
• The precise mechanisms driving these complications remain unclear.
• The endothelium is recognized as a primary target of radiation injury.

Purpose of the Study:

• To test the hypothesis that endothelium-dependent vasodilation is impaired in irradiated kidneys before hypertension onset.
• To investigate the role of endothelial dysfunction in radiation nephropathy.

Main Methods:

• Long-Evans rats underwent unilateral nephrectomy and irradiation to the remaining kidney.
• Renal blood flow (RBF) responses to endothelium-dependent (acetylcholine, bradykinin) and -independent (nitroprusside, norepinephrine, angiotensin II) agents were measured.
• Nitric oxide synthesis was blocked with nitro L-arginine methyl ester; prostaglandin synthesis was inhibited with indomethacin.

Main Results:

• Irradiated kidneys showed impaired RBF increases in response to endothelium-dependent vasodilators.
• Responses to endothelium-independent vasodilators and vasoconstrictors were unaltered.
• Blocking nitric oxide synthesis mimicked the blunted vasodilation in sham rats; indomethacin had no effect.

Conclusions:

• Renal irradiation induces endothelial dysfunction prior to the development of hypertension.
• The vascular smooth muscle cells appear to be spared from radiation injury.
• Endothelial dysfunction is a key factor in the pathogenesis of radiation nephropathy.