| Sign In to gain access to subscriptions and/or personal tools. |
The Morphology of Juxtaglomerular Cell Hyperplasia and Hypertrophy in Normotensive Rats and Monkeys Given an Angiotensin II Receptor AntagonistMerck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France
Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France
Merck Sharp & Dohme-Chibret Laboratories, Research Center, Department of Safety Assessment, BP 134, Route de Marsat, 63203 Riom, France
Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA
Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA
Merck Research Laboratories, Department of Safety Assessment, West Point, Pennsylvania 19486, USA L-694,492 (DUP 532), an angiotensin II (AII) receptor antagonist, was given orally at 125 mg/kg/day to rats and monkeys for up to 6 mo to assess the effects of the compound on juxtaglomerular (JG) cells. In rats, mild JG cell hypertrophy/hyperplasia occurred and was associated with a 12-fold increase in the bromodeoxyuridine-labeling index of JG cells and a 10-fold increase in renal renin content. Ultrastructurally, intermediate cells with characteristics of both smooth muscle cells and granulated renin-producing cells as well as hypertrophied renin-synthesizing cells were seen in the afferent arterioles. In monkeys, marked hypertrophy and hyperplasia were seen with an 80% increase in JG cell numbers, mitotic activity, and a greatly increased renin content compared 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-synthesizing cells, and cell proliferation. When treatment was discontinued, the renin-producing cells redeveloped the features of smooth muscle cells, but, as we have shown with enalapril (angiotensin-converting enzyme inhibitor), the increase in their number persists for at least 3 mo.
Key Words: Renin-angiotensin system • kidney • pharmacology • renin
Toxicologic Pathology, Vol. 23, No. 3,
606-619 (1995) This article has been cited by other articles:
|
|
|||||||||||||||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
