Search

An interaction between angiotensin II (Ang II) receptors and alpha 2-adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hypertensive rat (SHR) using quantitative receptor autoradiography and cardiovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC50 value of l-noradrenaline when competing for ([3H]p-aminoclonidine ([3H]PAC) binding sites, which reached a maximum of 400% with 10 nM of Ang II and was associated with a small decrease in the B0 value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC50 value of about 57%, and no change was observed in the B0 value. Saturation analysis also showed that Ang II (0.1 nM) increased the KD value of [3H]PAC in the WKY strain but in contrast decreased the KD value of [3H]PAC in the SHR. The Bmax value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced by l-noradrenaline coinjected in the NTS of the WKY rat. No effect was observed in heart rate. In the SHR no counteraction of the l-noradrenaline-induced vasodepressor effect was found, and in contrast a slight increase of the vasodepressor effect associated with a significant increase in the bradycardiac response was observed. The results give evidence for an antagonistic Ang II/alpha 2 receptor interaction in the cardiovascular part of the NTS of the WKY rat as previously observed in the Sprague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/alpha 2 receptor interaction enhances alpha 2 affinity and possibly alpha 2 receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.

The modulation of neuropeptide Y (NPY) receptors by alpha 2 receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arterial blood pressure and heart rate. The receptor autoradiographical experiments showed that clonidine (10 nM), a selective alpha 2 receptor agonist, induced a 59% increase in the B0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [125I]peptide YY ([125I]PYY)-binding sites in the presence of [Leu31, Pro34]NPY (100 nM), a selective NPY Y1 receptor agonist, to block the binding to NPY Y1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y2 receptor agonist, was used to block the binding to NPY Y2 receptors, clonidine (1-30 nM) did not affect the B0 value and the IC50 value of NPY(1-36) when competing for [125I]PYY-binding sites, suggesting that the stimulation of alpha 2 receptors can selectively increase the affinity of NYP(1-36) for the NPY Y2 receptor. Microinjections of threshold doses of adrenaline or clonidine into the Sol not only counteracted the vasopressor action of a close to ED50 dose of coinjected NPY(13-36), but also changed the vasopressor and tachycardic response produced by NPY(13-36) into a vasodepressor and bradycardic response. However, threshold doses of adrenaline or of clonidine microinjected into the Sol did not modify the vasodepressor responses to a close to ED50 dose of NPY(1-36) or of [Leu31, Pro34]NPY.(ABSTRACT TRUNCATED AT 250 WORDS)