Abstract
Neuropeptide Y (NPY), angiotensin II (Ang II) and adrenergic transmission lines in the nucleus tractus solitarii (NTS), the major relay nucleus involved in the cardiovascular reflex, play an important role in central cardiovascular control. The present work explored reciprocal interactions of NPY and Ang II receptor subtypes with a2-adrenoceptors in the NTS of the normotensive Sprague-Dawley rat (SD), the normotensive Wistar Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) by using a cardiovascular analysis, quantitative receptor autoradiography, immunocytochemistry and in situ hybridization techniques.
a2A-Adrenoceptors have been shown to be present in almost allcatecholaminergic neurons in the brainstem including the NTS. NPY Yl or AngII ATl receptor-like immunoreactivity (-LI) was found to be colocalized with tyrosine hydroxylase-LI in the NTS suggesting colocalization of these receptors with a2-adrenoceptors in catecholaminergic neurons of the NTS.
In the NTS of the SD, the NPY Yl and Y2 receptor agonists decreased the affinity and transduction of a2-adrenoceptors. In contrast, a2-adrenoceptor agonists increased NPY Y2 receptor affinity but reduced the NPY Y2 receptor functions, i.e., the NPY Y2 receptor-mediated cardiovascular actions and the NPY-induced c-Fos expression in the NTS. NPY Y2 receptor agonists reduced transduction over NPY Yl receptors in the NTS.
In the SHR, a2A-adrenoceptor mRNA levels and a2-adrenoceptor binding sites in the NTS were lower than those in the WKY. NPY in the NTS of the SHR had an increased potency to antagonize a2-adrenoceptor function. This suggests that abnormal NPY/a2-adrenergic receptor interaction may contribute to the development of hypertension.
In the NTS of the SD, activation of Ang II ATI receptors reduced the affinity and transduction of a2-adrenoceptors, whereas a2-adrenoceptor activation had the opposite effect on Ang II receptors. Ang II differentially regulates a2-adrenoceptors in the NTS of the WKY and the SHR. In the WKY, Ang II reduced the affinity and function of a2-adrenoceptors. In the SHR, however, Ang II increased them. This opposite effectin the SHR may be one compensatory mechanism to counteract the development of high blood pressure in the SHR.
In conclusion, the present work provides evidence for reciprocal interactions of NPY and Ang II receptors with a2-adrenoceptors in the NTS participating in cardiovascular regulation which are altered in relation to spontaneous hypertension.
