Angiotensin II acting on brain AT1 receptors induces adrenaline secretion and pressor responses in the rat

Abstract

Angiotensin II (AngII) plays important roles in the regulation of cardiovascular function. Both peripheral and central actions of AngII are involved in this regulation, but mechanisms of the latter actions as a neurotransmitter/neuromodulator within the brain are still unclear. Here we show that (1) intracerebroventricularly (i.c.v.) administered AngII in urethane-anesthetized male rats elevates plasma adrenaline derived from the adrenal medulla but not noradrenaline with valsartan- (AT1 receptor blocker) sensitive brain mechanisms, (2) peripheral AT1 receptors are not involved in the AngII-induced elevation of plasma adrenaline, although AngII induces both noradrenaline and adrenaline secretion from bovine adrenal medulla cells, and (3) i.c.v. administered AngII elevates blood pressure but not heart rate with the valsartan-sensitive mechanisms. From these results, i.c.v. administered AngII acts on brain AT1 receptors, thereby inducing the secretion of adrenaline and pressor responses. We propose that the central angiotensinergic system can activate central adrenomedullary outflow and modulate blood pressure.

Angiotensin II, a stress‐related neuropeptide in the CNS, facilitates micturition reflex in rats

“…Brain Ang II acts to induce several physiological responses, including stimulation of water and sodium intake, vasopressin secretion and BP increase by activating AT 1 receptors (Averill and Diz, ; Chen and Pan, ). We also previously demonstrated that centrally administered Ang II increases the release of adrenaline from the adrenal medulla in the rat, suggesting activation of the sympatho‐adrenomedullary system (Nakamura et al ., ). Moreover, our previous findngs showed that centrally administered Ang II at a dose that does not affect BP or the peripheral adrenaline levels shortens the intercontraction interval (ICI) by acting on the brain AT 1 receptors in rats (Kawamoto et al ., ).…”

A Stress-Related Peptide Bombesin Centrally Induces Frequent Urination through Brain Bombesin Receptor Types 1 and 2 in the Rat

“…In some experiments, acute bilateral adrenalectomy (ADX) [plus hydrocortisone (5 mg/kg per animal, i.m.)] was performed just before the cannulation by an abdominal midline incision (Shimizu et al, 2006;Nakamura et al, 2014). Subsequently, each rat was placed in a stereotaxic apparatus for the brain (SR-6R; Narishige, Tokyo, Japan) until the end of each experiment, as described previously by our laboratory (Shimizu et al, 2004).…”

Central angiotensin II type 1 receptor as a therapeutic target against frequent urination

“…The study showed chronic pretreatment with telmisartan (3‐30 mg/kg) suppressed central Ang II‐induced effects (drinking response, arterial pressure increase and release of vasopressin) . Change in BP by AT1 receptor antagonist administration might affect micturition reflex via sympathetic nerve activity . Current data showed that peripherally administered telmisartan (3 or 10 mg/kg) at doses which do not affect BP, suppressed the central Ang II‐induced ICI reduction in rats.…”

“…In addition, the previous report showed that centrally administered Ang II stimulated the release of adrenaline from the adrenal medulla in rats. This data suggests central Ang II activates the sympatho‐adrenomedullary system, a characteristic feature of the stress response. Moreover, different types of stress stimulate the Ang II release and also increase the expression of brain AT1 receptors .…”

“…17 Change in BP by AT1 receptor antagonist administration might affect micturition reflex via sympathetic nerve activity. 6,20 Current data showed that peripherally administered telmisartan (3 or 10 mg/kg) at doses which do not affect BP, suppressed the central Ang II-induced ICI reduction in rats. In contrast, peripherally administered valsartan (10 mg/kg) did not affect the central Ang II-induced ICI reduction in rats.…”