Role of losartan and MAPK pathway in the natriuresis induced by central stimul

This study investigated the effect of intracerebroventricular (ICV) administration of the angiotensin AT₁ receptor antagonist losartan on the natriuresis, pressor effect, and the mitogen-activated protein kinases (MAPK) activity in the rostroventrolateral medulla (RVLM) caused by ICV injection of either angiotensin II (ANG II) or carbachol. Losartan (20μg) was infused into the lateral ventricle before, during, and after infusions of either ANG II at 10 μg, or carbachol at 0.5 μg. ICV injection of ANG II or carbachol caused increases in urinary sodium excretion, arterial pressure, and the activity of MAPK in the RVLM. Increases in arterial pressure, Na⁺ excretion, and the activity of MAPK in the RVLM in response to ICV injection of ANG II were either abolished or attenuated by ICV injection of losartan. ICV injection of losartan did not reduce the increase in arterial pressure in response to ICV injection of carbachol, but it did attenuate the natriuretic response to ICV administration of carbachol. We conclude that an ICV dose of losartan that inhibits responses to ICV injection of ANG II also inhibits natriuresis, and the pressor response to ICV injection of carbachol. These results suggest that common neural pathways are involved in the responses induced by ICV administration of ANG II and carbachol. We propose that ICV injection of carbachol activates angiotensinergic and MAPK signal pathways in the central nervous system subserving the regulation of fluid and electrolyte balance and arterial pressure in rat.