Prenatal blockade of Ang II receptors affects neonatal rat hindbrain structure and receptor localization.

SUSANA I SÁNCHEZ; MARIA E ARCE; LB FUENTES; GLADYS M CIUFFO

Experimental Neurology

Elsevier

Lugar: United States; Año: 2009 vol. 220 p. 246 - 257

0014-4886

Angiotensin II (Ang II) receptor expression seems to be regulated during fetal and early postnatal life. Behavioral abnormalities in Ang II AT2 receptor knockout mice and the embryonic expression pattern of Ang II receptors in rats suggest a potential role on development. We evaluated the effect of stimulation/inhibition of Ang II receptors during pregnancy in hindbrain development, in offspring (postnatal days  P0, P8) of pregnant rats treated with saline, Ang II, Losartan or PD123319 (1 mg/kg/day). Receptor localization was studied by autoradiography, and its expression by RT-PCR. In P0 and P8 hindbrains, most structures expressed AT2 subtype: cerebellar cortex and nuclei, g7 (genu facial nucleus), IC (inferior colicullus), IO (Inferior Olive). In the cerebellar cortex, [125I]Ang II AT2 binding was predominant, while low AT1 binding was observed in adjacent layers of the cerebellar cortex. Blockade of AT2 receptors with PD123319 during late pregnancy increased binding in cerebellar nuclei and IO (p< 0.05) in P0 animals in correlation with increased AT2 receptor expression. Alterations in hindbrain morphology and binding persisted in P8 animals, suggesting that damage continues after prenatal exposure to drugs. The enlarged external granulose layer (EGL) in the cerebellar cortex of P0 pups treated with PD123319 and the lower binding at the EGL (p< 0.001), suggest either that a certain type of cells overproliferate or that cells do not differentiate/ migrate when AT2 receptors were blocked. These observations support the hypothesis of a role of Ang II AT2 receptors during hindbrain development, probably modulating apoptosis.