Renovascular hypertension: etiology and pathophysiology

Evidence from animal studies demonstrates that the renin-angiotensin (ANG II) system and sodium retention play major roles in experimental renovascular hypertension (RVH). Two basic models have been described. In the first, one-clip two-kidney Goldblatt hypertension, the ischemic kidney secretes renin, which leads to increased ANG II formation and hence elevation of blood pressure (BP). As BP rises, sodium excretion by the intact contralateral kidney increases (pressure natriuresis); therefore, there is no sodium retention. In the second, one-clip one-kidney Goldblatt hypertension, the contralateral kidney is removed. In this case the pressure natriuresis can no longer occur, and sodium retention occurs. The ensuing expansion of plasma volume inhibits renin secretion, so that in this model the renin level is normal or low. Following the clipping of the renal artery, renal blood flow and pressure are maintained distal to the stenosis by an ANG II-mediated vasoconstriction. This acts preferentially on the efferent glomerular arterioles, so that the ratio of preglomerular to postglomerular resistance is reduced, which helps to maintain glomerular filtration despite the reduced renal perfusion pressure. In the contralateral kidney the afferent arteriolar resistance is increased, probably as a direct result of exposure to the higher intrarenal arterial pressure. ANG II constricts the efferent arterioles in the same way as in the ischemic kidney, so that the ratio of preglomerular to postglomerular resistance is unchanged. When an angiotensin converting enzyme (ACE) inhibitor is given, the efferent arterioles vasodilate. In the ischemic kidney this may produce a reduction of glomerular filtration rate (GFR), which is not seen in the contralateral kidney. Unilateral RVH in humans corresponds closely to the animal model of one-clip two-kidney hypertension. Plasma renin activity is usually high, and converting enzyme inhibitors lower BP effectively. The increased renin is due exclusively to increased secretion of renin by the ischemic kidney, and is completely suppressed in the contralateral kidney. It is not clear whether bilateral RVH corresponds to the one-clip one-kidney model, but there is circumstantial evidence to suggest that both renin and volume factors may be involved. The majority of cases of human RVH are caused by atheroma, which is commonly bilateral, or by fibromuscular dysplasia. The former tends to be associated with atheroma elsewhere in the arterial tree, and often progresses to complete occlusion and renal failure. The latter occurs in younger patients, and almost never progresses to complete occlusion.