AT1 receptor blockade delays postlactational mammary gland involution: a novel role for the renin angiotensin system.

NAHMOD KA, WALTHER T, CAMBADOS N, FERNANDEZ N, MEISS R, TAPPENBECK N, WANG Y, RAFFO D, SIMIAN M, SCHWIEBS A, POZNER RG, FUXMAN BASS JI, POZZI AG, GEFFNER JR, KORDON EC, SCHERE-LEVY C.

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2012 vol. 26 p. 1982 - 1994

0892-6638

Angiotensin II (AngII), the main effector peptide of the renin-angiotensin system (RAS), participates in multiple biological processes, including cell growth, apoptosis, and tissue remodeling. Since AngII activates, in different cell types, signal transducing pathways that are critical for mammary gland postlactational regression, we investigated the role of the RAS during this process. We found that exogenous administration of AngII in mammary glands of lactating Balb/c mice induced epithelium apoptosis [2.9±0.5% (control) vs. 9.6±1.1% (AngII); P < 0.001] and activation of the proapoptotic factor STAT3, an effect inhibited by irbesartan, an AT(1) receptor blocker. Subsequently, we studied the expression kinetics of RAS components during involution. We found that angiotensin-converting enzyme (ACE) mRNA expression peaked 6 h after weaning (5.7-fold; P