Brain Research 883 (2000) 148–156 www.elsevier.com / locate / bres Interactive report Characterisation of vasopressin V , angiotensin AT and AT receptor 1A 1 2 distribution and density in normotensive and hypertensive rat brain 1 stem and kidney: effects of restraint stress * Stuart J. McDougall, Carlie A. Roulston, Robert E. Widdop, Andrew J. Lawrence Department of Pharmacology, Monash University, Wellington Rd., Clayton, Victoria, Australia 3168 Accepted 14 September 2000 Abstract In the present study, we have examined neurochemical correlates that may be involved in the differential cardiovascular responses observed in normotensive and hypertensive rats during stress. Using a restraint stress paradigm, both normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) underwent acute (1 h restraint in a perspex tube), chronic (1 h restraint for ten consecutive days) or no restraint (control) stress. Following cessation of restraint, rats were processed by incubating sections of brain stem and kidney 125 125 1 8 with [ I]-HO-LVA (0.03 nM) or [ I]Sar Ile -AngiotensinII (0.5 nM), in the presence of PD123319 (10 mM) or losartan (10 mM), to determine the distribution and density of vasopressin V , angiotensin AT and AT receptors, respectively. Analysis of autoradiograms 1A 1 2 indicated changes in the density of radioligand binding in acutely and chronically-stressed rats, as compared to controls. For example, V 1A binding in the medial nucleus tractus solitarius (SolM) decreased in the WKY but increased in the SHR. AT binding in SolM did not 1 significantly change in the WKY but decreased in the SHR with repeated restraint. In kidney slices, AT binding decreased with stress in 1 the WKY ( 217%) but increased in SHR (110–15%). AT binding in the kidney showed a pattern similar to that of AT binding in SHR, 2 1 but not WKY. Graded increases in V binding were measured in kidney medulla and cortex of both strains (150–60% with chronic 1A restraint). These results suggest that physiological adaptation to restraint is associated with specific changes in V , AT and AT receptor 1A 1 2 density within brain nuclei and kidney.  2000 Elsevier Science B.V. All rights reserved. Theme: Neurotransmitters, modulators, transporters, and receptors Topic: Receptor modulation, up- and down-regulation Keywords: Restraint; WKY; SHR; Angiotensin; Vasopressin; Receptor autoradiography 1. Introduction telemetry, that Spontaneously Hypertensive rats (SHR) have an impaired capacity to cope with the stress-induced Acute stressors, such as restraint are well characterised tachycardia compared to normotensive Wistar–Kyoto rats to cause immediate and profound tachycardia; however, (WKY) [22]. Considering that coping (adaptation or such responses may diminish with subsequent stress habituation) occurs due to changes within the central encounters [6]. Associated with this adaptation are also nervous system (CNS) nuclei that regulate the stress alterations in the activity of the hypothalamo–pituitary– response [15], it would appear that SHR may have a adrenal axis (HPA) and sympatho-adrenal system (SAS) reduced plasticity within the CNS compared to WKY. [14,17]. We have recently demonstrated, using radio- Central control of the cardiovascular system is achieved via a complex network of interconnected nuclei. While the basic control is primarily mediated at the level of the 1 Published on the World Wide Web on 2 October 2000. medulla oblongata, significant supramedullary modulation *Corresponding author. Tel.: 161-3-9905-4855; fax: 161-3-9905- also occurs [8]. For example, the locus coeruleus (LC) 5851. makes up a large portion of the central noradrenergic E-mail address: andrew.lawrence@med.monash.edu.au (A.J. Law- rence). system, which is thought to play an important role in the 0006-8993 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02917-6