Adenylate cyclase-cyclic AMP-phosphodiesterase system in microdissected brain areas of normotensive and spontaneously hypertensive rats.

The topographical distribution of the adenylate-cyclase-cyclic adenosine monophosphate-phosphodiesterase system was investigated in specific brain areas of rats, and compared with spontaneously hypertensive rats. In normotensive animals, brain cyclic adenosine monophosphate levels were quite uniform (between 7.14 and 13.04 pmol/mg protein) with highest concentrations in catecholamine-containing cell groups. In contrast, the distribution of basal adenylate cyclase and phosphodiesterase activity is not uniform. The unstimulated adenylate cyclase activity was very low in the striatum and catecholamine-containing cell groups in the medulla oblongata (A1C1-cell groups) and very high in the central gray matter and the cerebellum, where the lowest phosphodiesterase activities were measured. In spontaneously hypertensive rats, altered cyclic adenosine monophosphate levels were found in 17 of 36 brain areas investigated in comparison to those of normotensive rats. Increased concentrations were found in regions which are known to participate in the central regulation of blood pressure (nucleus of the solitary tract, A1C1 catecholaminergic cell groups in the ventrolateral medulla oblongata, locus coeruleus) and in the periaqueductal central gray matter, the hippocampus and the cingulate cortex. Lower levels were measured only in hypothalamic nuclei, especially in the paraventricular and dorsomedial nucleus. No significant differences in basal adenylate cyclase activity were found in spontaneously hypertensive rats compared with Wistar-Kyoto control rats, while phosphodiesterase activity was generally higher in spontaneously hypertensive rats, most significantly in the medulla oblongata. Present data show that characterization of the adenylate cyclase-cyclic adenosine monophosphate-phosphodiesterase system helps to localize structural and/or functional differences between the spontaneously hypertensive rat and its normotensive control rat and indicate that more than one functional system is affected in spontaneous hypertension.