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

St. Louis University School of Medicine, St. Louis, Missouri Submitted 21 August 2007 ; accepted in final form 21 April 2008 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 AT 1 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 AT 1 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 GABA A 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 AT 1 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 AT 1 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. AT 1 receptor; cocaine; anteroventral third ventricle region; systemic vascular resistance; cardiovascular response variability Address for reprint requests and other correspondence: M. M. Knuepfer, Dept. of Pharmacological and Physiological Science, St. Louis Univ. School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104 (e-mail: knuepfmm{at}slu.edu )