Increased angiotensin II binding affinity in the nucleus tractus solitarius of spontaneously hypertensive rats.

Abstract

Angiotensin II (Ang) binding kinetics were determined in discrete brainstem nuclei of 14-week-old spontaneously hypertensive rats (SHR) and normotensive WistarKyoto rats (WKY) by a quantitative autoradiographic technique. Tissue sections were incubated with 125I-labeled [sarcosine-l]Ang, and results were analyzed by computerized densitometry and comparison to '25I-labeled standards. A single class of high-affinity binding sites was identified in the nucleus tractus solitarius, the area postrema, and the inferior olivary nuclei of both SHR and WKY rats. Ang binding affinity was significantly greater in the nucleus tractus solitarius of SHR compared to normotensive WKY rats (0.27 ± 0.06 x 109 M-1 in WKY rats vs. 0.59 ± 0.15 x 109 M-1 in SHR), with no apparent changes in the maximum binding capacity of this area. There were no changes in the Ang binding kinetics of the area postrema or the inferior olivary nuclei. Our results suggest that central Ang activity is altered in established hypertension in a brainstem area of SHR associated with peripheral cardiovascular control.After the identification of components ofa central renin-angiotensin system, angiotensin II (Ang) was linked with centrally mediated cardiovascular effects (1, 2). Specific receptors for Ang have been localized to brain areas involved in cardiovascular regulation, including the nucleus tractus solitarius, area postrema, locus coeruleus, and dorsal motor nucleus of the vagus (3, 4). Additionally, Ang immunoreactive cells and fibers have been identified in the rat central nervous system, also in areas associated with peripheral cardiovascular control (5). Microinjections of Ang into the nucleus tractus solitarius have been shown to produce dose-dependent increases in blood pressure that are similar to increases seen after intraventricular injection of Ang (6). These studies link central Ang activity with cardiovascular control.Evidence has also shown that alterations in central Ang activity occur during the pathogenesis of spontaneous hypertension. Angiotensin-converting enzyme antagonists, such as captopril, lower blood pressure in spontaneously hypertensive rats (SHR), with a greater reduction occurring after intraventricular administration (7). Ang levels have been shown to be increased in the brain of SHR, including brain areas known to affect cardiovascular function (8). These results suggest that Ang hyperactivity may contribute to the maintenance of hypertension in SHR. The purpose of this study was to determine ifbrainstem Ang receptor binding kinetics are altered in spontaneous hypertension, a change that could contribute to the hyperactivity of the central Ang system in these animals. (9,10). METHODSTo allow for quantitation of ligand binding, sets of 1251I labeled standards were prepared as described for 3H-labeled standards (11). Known amounts of 1251 in increasing concentrations were thoroughly mixed with a brain paste, mounted as blocks on specimen holders, and frozen. Sections (16 ,um) were cut on a cryostat at -14°C and t...

Effects of renovascular hypertension on reproductive function in male rats

“…Apart from its role in the regulation of blood pressure RAS has been implicated in the regulation of reproduction (Ganong, 1995;Keaton and Clark, 1998;Breigeiron et al, 2002;Speth et al, 2003). Ang II, detected by immunohistochemistry, as well as Ang II receptors, detected by in situ hybridization and binding techniques, had been found in brain areas that exert control over reproductive function (Lind et al, 1985;Jöhren et al, 1997a,b), such as the medial preoptic area (MPOA) and medial amygdaloid nucleus (MeA) (Halbach and Albrecht, 1998), and in neural sites that act on blood pressure control, such as the nucleus of the solitary tract (Plunkett and Saavedra, 1985) and subfornical organ (SFO) . In experimental hypertension, the SFO is necessary for the full hypertensive response to chronic Ang II administration Collister and Hendel, 2005).…”

Effect of a Reduction in Sodium Intake on Cold-Induced Elevation of Blood Pressure in the Rat

“…Furthermore, the state of the receptors for Ang I1 in the diencephalon of rats is known to be correlated directly with the dipsogenic responsiveness to Ang 11, whether administered either centrally or peripherally (30). In addition, several studies suggest a direct correlation between the state of receptors for Ang I1 in the diencephalon and the development of hypertension; i.e., up-regulation of receptors for Ang I1 has been linked to the inductions of both deoxycorticosterone acetate-salt and spontaneously induced hypertensions (30)(31)(32)(33). The results of the present study are at least consistent with an up-regulation of central Ang I1 receptors in the cold- sion is further suggested by the fact that chronic administration of captopril, spironolactone, or clonidine, which inhibit the renin-angiotensin-aldosterone system at different levels, can either prevent or ameliorate the development of hypertension (1 2, 13).…”

Reporter mouse strain provides a novel look at angiotensin type-2 receptor distribution in the central nervous system

“…Although the present studies indicate that AT2R are likely localized to GABAergic neurons within this region, the impact of AT2R activation on their neuronal activity is yet to be determined. That being said, it has been documented that angiotensin receptor binding and expression are sensitive to hypertensive stimuli (Plunkett and Saavedra 1985) and that manipulation of the RAS within the NTS regulates the baroreflex and blood pressure (Eshima et al 2000; Polson et al 2007; Shan et al 2013; Wang et al 2007), as well as indices of GABA signaling (Zhang et al 2009). …”