THE MORPHOLOGY OF JUXTAGLOMERULAR CELL HYPERPLASIA AND HYPERTROPHY INNORMOTENSIVE RATS AND MONKEYS GIVEN AN ANGIOTENSIN-II RECEPTOR ANTAGONIST

L-694,492 (DUP 532), an angiotensin II (AII) receptor antagonist, was given orally at 125 mg/kh/day to rats and monkeys for up to 6 mo to as sess the effects of the compound on juxtaglomerular (JG) cells. In rat s, mild JG cell hypertrophy/hyperplasia occurred and was associated wi th a 12-fold increase in the bromodeoxyuridine-labeling index of JG ce lls and a 10-fold increase in renal renin content. Ultrastructurally, intermediate cells with characteristics of both smooth muscle cells an d granulated renin-producing cells as well as hypertrophied renin-synt hesizing cells were seen in the afferent arterioles. In monkeys, marke d hypertrophy and hyperplasia were seen with an 80% increase in JG cel l numbers, mitotic activity, and a greatly increased renin content com pared to controls. Three mo after drug withdrawal, an increased number of cells remained, which showed features of smooth muscle cells with essentially no renin. These results show that AII receptor antagonism stimulates increased renal renin production by hypertrophy of existing granulated cells, metaplasia of smooth muscle cells to renin-synthesi zing cells, and cell proliferation. When treatment was discontinued, t he renin-producing cells redeveloped the features of smooth muscle cel ls, but, as we have shown with enalapril (augioteusin-converting enzym e inhibitor), the increase in their number persists for at least 3 mo.