Vascular angiotensin AT1 receptor neuromodulation in fetal programming of hypertension

Abstract

Fetal stress increases the susceptibility to cardiovascular diseases in adult age, including hypertension, a process known as fetal programming of hypertension (FPH). This study intends to investigate the interplay between vascular sympathetic nervous system (SNS) and RAS, namely the neuromodulatory role exerted by Angiotensin II (Ang II) receptor-1 (AT1) in FPH, and respective contribution for hypertension.

Methods: 6-month old Sprague-Dawley offspring from mothers fed ad-libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. Sympathetic neurotransmission was studied in mesenteric/tail arteries and mesenteric veins by electrically-evoked [³H]-noradrenaline release experiments using RAS drugs. AT1 receptors in sympathetic nerves of mesenteric arteries were investigated by immunohistochemistry and Laser Scanning Confocal Microscopy.

Results: Ang II facilitated noradrenaline release in the vessels studied from MUN and CONTROL rats. Losartan induced a tonic facilitation only in MUN vessels. Sympathetic innervation was larger in MUN versus CONTROL vessels. AT1 receptors on sympathetic nerves were present in higher amounts in MUN versus CONTROL vessels.

Conclusions: Findings support that FPH is associated with a vascular hyper-sympathetic activation, involving a tonic facilitation of prejunctional AT1 receptors by endogenous Ang II, which can justify, at least in part, the development of hypertension.

Keywords: ANG II; AT1 receptors; Fetal programming of hypertension; RAS; Sympathetic nerves.