INHIBITION OF ANGIOTENSIN II RECEPTORS DURING PREGNANCY INDUCES

SÁNCHEZ SI; SELTZER AM; FUENTES LB; FORNERIS LM; CIUFFO GM

EUROPEAN JOURNAL OF PHARMACOLOGY

Elsevier

Año: 2008

0014-2999

Abstract: Evidence suggests that Angiotensin II (Ang II) plays an important role in the complex process of renal organogenesis. Rat kidney organogenesis starts between E13-14 and lasts up to two weeks after birth. The present study demonstrates histologic modifications and changes in receptor localisation in animals born from mothers treated with Ang II, Losartan or PD123319 (1.0 mg/kg/day) during late pregnancy. Ang IItreated animals exhibited very well developed tubules in the renal medulla in coincidence with higher AT1 binding. Control animals exhibited angiotensin AT2 binding in the outer stripe of the outer medulla, while in the Ang II-treated animals binding was observed to the inner stripe. In these animals at postnatal day (PND) 8, the nephrogenic zone (NZ) contained fewer immature structures, and more developed collecting tubules than control animals. Treatment with Losartan resulted in severe renal abnormalities. At PND0 and PND8, glomeruli exhibited altered shape and enlarged Bowman spaces, in concordance with a loss of [125I]Sar1Ang II binding in the cortex. Blockade with PD123319 led to an enlarged NZ with increased number of immature glomeruli, and less glomeruli in the juxtamedullary area. Autoradiography showed a considerable loss of AT1 binding in the kidney cortex of PD123319-treated animals at both ages. The present results show for the first time histomorphological and receptor localisation alterations following treatment with low doses of Losartan and PD123319 during pregnancy. These observations confirm previous assumptions that in the developing kidney Ang II exerts stimulatory effects through AT1 receptors that might be counterbalanced by angiotensin AT2 receptors.