A Comparison of CNS Angiotensin II Binding in the Hypothalamus???Thalamus???Septum???Midbrain Region of Developing Spontaneously Hypertensive and Normotensive Rats

Abstract

Specific angiotensin II (ANG II) binding was studied in brain homogenates from the hypothalamus-thalamus-septum-midbrain (HTSM) region of age-matched 4-, 8-, 12- and 16-week spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using 125I-angiotensin II. Scatchard analysis revealed that the dissociation constants (Kd) ranged from 0.36 to 0.73 nmol/l, although these values were not significantly different at any given age period between the SHR and WKY rats. In contrast, a statistically significant increase in ANG II receptor binding was seen between the SHR and WKY rat at 4 weeks of age. However, this difference was not observed at older age periods. Furthermore, both the SHR and WKY rat showed a decrease in ANG II receptor levels during development, with the most marked reductions occurring between 12 and 16 weeks of age for both strains. These findings suggest that ANG II receptors in the HTSM region of both the SHR and WKY rat are down-regulated during development, that receptor loss is more significant in the SHR than in its normotensive control and that binding capacity differences between the two strains are only seen before the onset of measureable increases in the arterial pressure of the SHR. We conclude that there is a significant difference in the ANG II binding capacity during the development of hypertension in the SHR as compared with the WKY rat and therefore it may play a role in the pathogenesis of this disorder.