Chronic systemic infusion of Angiotensin II upregulated AT1 receptor expression in the paraventricular nucleus and subfornical organ of rats by activating intracellular p44/42 MAPK and JNK signaling pathways.
p-value: p=<0.05
ANG II type 1 receptors (AT(1)R) mediate most of the central effects of ANG II on cardiovascular function, fluid homeostasis, and sympathetic drive. The mechanisms regulating AT(1)R expression in the brain are unknown. In some tissues, the AT(1)R can be upregulated by prolonged exposure to ANG II. We examined the hypothesis that ANG II upregulates the AT(1)R in the brain by stimulating the intracellular mitogen-activated protein kinase (MAPK) signaling pathway. Using molecular and immunochemical approaches, we examined expression of the AT(1)R and phosphorylated MAPK in the paraventricular nucleus of the hypothalamus (PVN) and the subfornical organ (SFO) of rats receiving a chronic (4-wk) subcutaneous infusion of ANG II (0.6 microg/h) or saline (vehicle control), with or without concomitant (4-wk) intracerebroventricular (ICV) infusions of MAPK inhibitors or the AT(1)R blocker losartan. Subcutaneous infusion of ANG II markedly increased phosphorylation of MAPK and expression of AT(1)R mRNA and protein and AT(1)R-like immunoreactivity in the PVN and SFO. ANG II-induced AT(1)R expression was blocked by ICV infusion of the p44/42 MAPK inhibitor PD-98059 (0.025 microg/h) and the JNK inhibitor SP-600125 (0.125 microg/h), but not by the p38 MAPK inhibitor SB-203580 (0.125 microg/h). Upregulation of the AT(1)R in the PVN and SFO by peripheral ANG II was abolished by ICV losartan (10 microg/h). The data indicate that blood-borne ANG II upregulates brain AT(1)R by activating intracellular p44/42 MAPK and JNK signaling pathways.
Wei et al. (Sat,) conducted a other in Normal physiological state (investigating AT1 receptor regulation) (n=144). Angiotensin II with or without MAPK inhibitors or losartan vs. Saline (vehicle control) was evaluated on AT1R mRNA and protein expression in the paraventricular nucleus (PVN) and subfornical organ (SFO) (p=<0.05). Chronic systemic infusion of Angiotensin II upregulated AT1 receptor expression in the paraventricular nucleus and subfornical organ of rats by activating intracellular p44/42 MAPK and JNK signaling pathways.