Healy D P, Rettig R, Nguyen T, Printz M P
Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029.
Brain Res. 1989 Apr 10;484(1-2):1-12. doi: 10.1016/0006-8993(89)90343-0.
The experiments reported here were designed to examine whether angiotensin II (AII) receptors in the rat solitary-vagal area (SVA) are associated with the neuronal components of the baroreceptor reflex. AII receptors were characterized both in membrane preparations from the rat brainstem and by in vitro autoradiography using the radiolabeled AII antagonist [125I]Sar1,Ile8-AII([ 125I]SI-AII). Saturation analysis of [125I]SI-AII binding to membrane preparations from rat brainstem indicated binding to two high affinity sites (Kd1 0.32 nM and Bmax1 5.10 fmol/mg protein, Kd2 0.99 nM and Bmax2 7.94 fmol/mg protein). The rank order competition by unlabeled angiotensin peptides (SI-AII greater than AII greater than AIII greater than AI) in both membrane preparations and by quantitative autoradiography was consistent with the labeling of the brain AII receptor. Autoradiography of the [125I]SI-AII binding in sections through the SVA revealed that the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) were heavily labeled. Bilateral sinoartic denervation, which disrupts primary baroreceptor afferents, resulted in a small decrease in [125I]SI-AII binding in the rostral and intermediate NTS and DMV. Unilateral nodose ganglionectomy, which disrupts completely the vagal afferent input to the NTS and produces retrograde degeneration of the vagal efferent neurons in the DMV, resulted in a marked decrease in [125I]SI-AII binding at all levels of the ipsilateral NTS and 56% decrease within the ipsilateral DMV. These results indicate that AII receptors within the SVA are distributed heterogeneously, with a large portion associated with vagal afferent fibers in the NTS and vagal efferent neurons of the DMV, and a small but significant portion associated with baroreceptor afferents. The majority of AII receptors in the NTS, however, were not affected by these surgical interventions and therefore appear to be located on intrinsic interneurons or non-vagal afferents in the NTS.
