Juncos, Luis I.

Increased lifespan in the last few decades has substantially changed the scenario for renal artery stenosis. Indeed, because older populations show a higher prevalence of atherosclerotic disease, the incidence of atheromatous renal artery stenosis has also increased. Intuitively, one could surmise that stenosis removal should void both the hypertension and the kidney damage resulting from the obstructive stenosis. Surprisingly, a number of important clinical trials have failed to show the reversion seen in experimental models. The reasons for these differences may be linked to chronicity and inflammation associated with the atherosclerotic lesion. However, the failure to obtain a favorable response may also be related to abnormalities in the contralateral kidney. Indeed, this apparently normal kidney should work to compensate the hemodynamic effects of the ipsilateral stenosed kidney. Instead, structure and function in the contralateral kidney can be altered in renal artery stenosis to the point that this nonstenotic kidney may sustain both, hypertension and progressive kidney disease. Certainly, comparing the effects of clip removal in the Goldblatt model to angioplasty in clinical settings with atherosclerotic lesions may be totally inappropriate. Nevertheless, there remain certain clinical situations such as bilateral renal arterial disease, congestive heart failure, and progressive renal failure, where angioplasty may be an alternative. These approaches however are yet to be tested.

AbstractWhile arterial hypertension and renal dysfunction are well recognized complications of renal irradiation, the mechanisms that trigger the development of these complications are unknown. Recently, it was reported that the endothelium is a major target in radiation injury. Because dysfunction of the endothelial cells may lead or contribute to the development of hypertension and renal dysfunction in radiation nephropathy, we tested the hypothesis that endothelium-dependent vasodilation is impaired in radiated kidneys prior to the onset of hypertension. To test this hypothesis, we used Long-Evans rats that had undergone left nephrectomy (3 weeks earlier) and irradiation (3000 r’s) to the right kidney 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 oxide synthesis with nitrol-arginine methyl ester in sham rats mimicked the blunted responsiveness of the irradiated rats, whereas indomethacin (an inhibitor of prostaglandin synthesis) had no effect on either sham or irradiated rats. Finally, the RBF responses to the endothelium-independent vasoconstrictors, norepinephrine and angiotensin II, were not altered in the irradiated kidneys. These results suggest that renal irradiation causes endothelial dysfunction (prior to the onset of hypertension) but spares the vascular smooth muscle cells.