title: Evidence for a differential modulation of the alpha-2 adrenoceptors by angiotensin II in the nucleus tractus solitarii of the spontaneously hypertensive and the Wistar-Kyoto normotensive rats.
abstract: 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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D R
authors.initials: DR
authors.lastname: Fior
authors.forename: S N
authors.initials: SN
authors.lastname: Yang
authors.forename: U
authors.initials: U
authors.lastname: Ganten
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D005069:Evaluation Studies as Topic; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012016:Reference Values; D017552:Solitary Nucleus / Q000378:metabolism*
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D000804:Angiotensin II; D009638:Norepinephrine