title: 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.
authors.affiliation: St. Louis University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schwartz
authors.forename: Nichole S
authors.initials: NS
authors.lastname: Reilly
authors.forename: Mark M
authors.initials: MM
authors.lastname: Knuepfer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002404:Catheterization / Q000592:standards; D003042:Cocaine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D011301:Preoptic Area / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D044140:Receptor, Angiotensin, Type 1; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D016291:Dizocilpine Maleate; D003042:Cocaine; D019808:Losartan