Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress

Abstract

The brain renin-angiotensin system plays an important role in the regulation of arterial pressure in response to stress, in part due to activation of AT1 receptors in the hypothalamic median preoptic nucleus (MnPO) by endogenous angiotensin II (ANG II). N-methyl-d-aspartate (NMDA) receptors are also involved in the angiotensinergic signaling pathway through the MnPO. We investigated whether AT1 and NMDA receptors in the MnPO are responsible for variable hemodynamic response patterns to stress. Cocaine or startle with cold water evoked a pressor response in Sprague-Dawley rats due, in some rats [vascular responders (VR)], to a large increase in systemic vascular resistance (SVR) and, in other rats [mixed responders (MR)], to small increases in SVR and cardiac output (CO). Microinjection of the GABAA agonist muscimol into the MnPO to block synaptic transmission attenuated the cocaine- or stress-induced increase in SVR and the decrease in CO seen in VR without altering either response in MR. Likewise, administration of either an AT1 receptor antagonist, losartan, or an NMDA receptor antagonist, MK-801, attenuated the increase in SVR and the decrease in CO in VR in response to either cocaine (losartan and MK-801) or startle with cold water (losartan) without altering either response in MR. We propose that the MnPO is responsible for greater SVR responses in VR and that AT1 and NMDA receptors play an important role in greater SVR responses in VR. These data provide additional support for the critical role of the MnPO in cardiovascular responses to stress.

Micro-Positron Emission Tomography Imaging of Rat Brain Metabolism during Expression of Contextual Conditioning

“…Both the nucleus accumbens (Westbrook et al, 1997;Pezze and Feldon, 2004;Martinez et al, 2008) and septal nucleus (Beck and Fibiger, 1995;Sparks and LeDoux, 1995;Calandreau et al, 2007;Reis et al, 2010) have at times been implicated in contextual conditioning, even though their exact roles remain unclear. The preoptic area seems to play a role in defensive and anxious behaviors (Briski and Gillen, 2001;McGregor et al, 2004;Salomé et al, 2004;Schwartz et al, 2008), but we found no studies providing direct evidence for its involvement in contextual conditioning.…”

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis

“…Pharmacological inhibition of AT 1 or NMDA receptors within the MnPO reduces the vasoconstrictor responses to cocaine or ice cold startle in a subgroup (vascular responders) of Sprague–Dawley rats, showing a role for the MnPO in stress‐mediated hemodynamic responses (Schwartz et al . ). Further, there is evidence to show that the MnPO relays signals from angiotensin‐sensitive neurones in the subfornical organ to the PVN (Tanaka et al .…”

Brain angiotensin AT1 receptors as specific regulators of cardiovascular reactivity to acute psychoemotional stress

“…Several hypothalamic and brain stem regions associated with autonomic regulation have been implicated in the central pressor actions of AngII during stress. Microinjection of losartan and saralasin directly into anterior and dorsomedial hypothalamic nuclei reduced the pressor and sympathoexcitatory effects of various psychological stressors in rats 21,24,25 . Similarly, microinjection of the highly specific AT 1 receptor antagonist candesartan into the dorsomedial hypothalamus (DMH) dose‐dependently reduced the pressor effect of air‐jet stress in rabbits 26 .…”

“…Microinjection of losartan and saralasin directly into anterior and dorsomedial hypothalamic nuclei reduced the pressor and sympathoexcitatory effects of various psychological stressors in rats. 21,24,25 Similarly, microinjection of the highly specific AT 1 receptor antagonist candesartan into the dorsomedial hypothalamus (DMH) dose-dependently reduced the pressor effect of air-jet stress in rabbits. 26 It is conceivable that AngII is also an important stress mediator in the rostral ventrolateral medulla (RVLM), a region that is critically implicated in sympathetic regulation 27 and that contains a high density of AT 1 receptors.…”