Quantitative autoradiography of angiotensin II receptors in the SHR brain

Several lines of evidence indicate brain angiotensin II is associated with the elevation of blood pressure seen in the spontaneously hypertensive rat (SHR). These include an increased pressor response to intracerebroventricularly administered angiotensin II and a reduction of blood pressure in response to centrally administered angiotensin II receptor antagonists. Using quantitative receptor autoradiography, we have detected greater angiotensin II receptor binding in a number of discrete brain nuclei of the 6-week-old SHR when compared to age-matched Wistar-Kyoto controls. Tissue sections from various brain regions were labeled with [125I]-angiotensin II according to a previously described method. Autoradiograms were generated by apposing the labeled tissue sections to LKB Ultrofilm along with brain paste standards which contained known amounts of [125I]. Quantitation of the binding, utilizing computer-assisted microdensitometry, indicated greater [125I]-angiotensin II binding in several brain areas implicated in cardiovascular control including the subfornical organ, nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, supraoptic nucleus and the organum vasculosum of the lamina terminalis. Scatchard analysis of the binding in the nucleus of the solitary tract indicated an increased receptor number (Bmax) was responsible for the change while binding in two forebrain structures, the subfornical organ and supraoptic nucleus, showed alterations in receptor number and affinity (Kd). Several other brain regions, unrelated to cardiovascular control, exhibited no change in [125I]-angiotensin II binding. Since the increased receptor binding was present primarily in brain regions related to cardiovascular control, we conclude that an increased angiotensin II receptor affinity and density is indicated as a factor in the etiology of the high blood pressure seen in the SHR.