Measurement of immunoreactive angiotensin II levels in microdissected brain nuclei from developing spontaneously hypertensive and Wistar Kyoto rats

Levels of immunoreactive angiotensin II (ANG II) were measured in specific microdissected nuclei from the brains of newborn (NB; less than 1 week of age), 4-, 8-, and 12-week-old spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, Wistar Kyoto (WKY) rats, using a sensitive radioimmunoassay. The structures investigated included the paraventricular nucleus of the hypothalamus (PVH), the nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (DMN of X), the locus coeruleus (LC), and the A1 region of the medulla. A section of cerebellar cortex was used as a control. Although ANG II was detected in each of the nuclei examined, there were no differences in the ANG II contents of any of these structures between young (NB and 4 week old) SH and WKY rats. However, by 8 weeks of age, the SHR had significantly higher ANG II levels in the PVH, NTS, and DMN of X than its normotensive control, and at 12 weeks of age, significantly higher ANG II levels were observed in the PVH, NTS, DMN of X, and LC of the SHR compared to those in the WKY. During the developmental period under investigation, both strains revealed increases in the ANG II content of all nuclei except for the LC, where the ANG II levels decreased with age. No detectable ANG II was found in the cerebellar cortex of either strain at any age. Since the brain and brain stem nuclei examined in this investigation have been implicated in the neural control of cardiovascular function, we conclude that the differences in ANG II levels between SH and WKY rats during development support the postulated role for ANG II in the pathogenesis of hypertension in the SH rat model.