THE EFFECTS OF ZENECA ZD8731, AN ANGIOTENSIN-II ANTAGONIST, ON RENIN EXPRESSION BY JUXTAGLOMERULAR CELLS IN THE RAT - COMPARISON OF PROTEINAND MESSENGER-RNA EXPRESSION AS DETECTED BY IMMUNNOHISTOCHEMISTRY ANDIN-SITU HYBRIDIZATION

Changes in the mRNA and protein expression of renin-secreting cells in the juxtaglomerular apparatus (JGA) were examined in the rat followin g administration of ZENECA ZD8731, an angiotensin II receptor antagoni st. Doses of 0 or 90 mg/kg were administered daily by gavage for 26 wk . JGA hypertrophy was apparent in histological sections. Immunohistoch emistry demonstrated an increase in the number of renin-containing cel ls in both the afferent arterioles and the interlobular arteries. Simi larly, renin mRNA expression, demonstrated by in situ hybridization, h ad extended to more proximal segments of the afferent arterioles and w as also present in efferent arterioles and interlobular arteries. In c onclusion, JGA hypertrophy occurred as a result of antagonism of the a ngiotensin II receptor. Associated with JGA hypertrophy was increased expression of both renin and renin mRNA, indicative of stimulated reni n synthesis caused by an exaggerated pharmacological response of renin -secreting cells to the loss of feedback inhibition by angiotensin II.