title: Metoprolol restores expression and vasodilatation function of AT2R in spontaneously hypertensive rats.
abstract: Angiotensin II type 2 receptor (AT2R) is thought as an important regulatory target during antihypertensive treatment but its role in vasomotor regulation remains controversial. The interactional relationship between the sympathetic nervous systems and the renin-angiotensin-aldosterone system (RAS) has been revealed but poorly investigated. This work was designed to explore the effect of metoprolol (MET) treatment on the RAS, especially the expression and vasomotor function of AT2R, in spontaneously hypertensive rats (SHR). The results showed that upregulated renin activity and Ang II concentration of plasma in SHR were inhibited by MET treatment. In isolated superior mesenteric arteries from both Wistar-Kyoto rats and SHR, Ang II perfusion induced vasodilatation after AT1R inhibition by telmisartan, although the vasodilatation was harmed in SHR. Furthermore, AT2R inhibitor PD123319 arrested the vasodilatation induced by Ang II. SHR received MET exerted improved vasodilatation mediated by AT2R (47.29% ± 5.16% vs. 24.99% ± 4.93% for MET and SHR, respectively; P < 0.05). Western blot analysis showed that MET restored expression of AT2R in SHR, which may contribute to MET's antihypertensive effect. These results suggested an impact of β-adrenergic blocker on RAS and supported an important role of AT2R in antihypertensive treatment.
authors.affiliation: *Center of Clinical Pharmacology, Third Xiangya hospital, Central South University, Changsha, China; †Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China; ‡Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China; and §Intensive Care Unit, Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Huang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Tang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D000077333:Telmisartan; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D012083:Renin; D008790:Metoprolol; D000077333:Telmisartan