Gallardo-Ortíz I A, Rodríguez-Hernández S N, López-Guerrero J J, Del Valle-Mondragón L, López-Sánchez P, Touyz R M, Villalobos-Molina R
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico.
Departamento de Farmacología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
Auton Autacoid Pharmacol. 2015 Sep;35(3):17-31. doi: 10.1111/aap.12035.
The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1 -adrenoceptors (α1 -ARs) expression was explored. Alzet(®) minipumps filled with Ang II (200 ng kg(-1) min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective α1D -AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased α1D -ARs without modifying the other α1 -ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1 Rs and α1D -ARs. Angiotensin II-induced α1D -AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a α1D -AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation.
探讨了持续输注血管紧张素II（Ang II）对动脉血压、血管肥大和α1-肾上腺素能受体（α1-ARs）表达的体内效应。将充满Ang II（200 ng kg(-1) min(-1)）的Alzet(®)微型泵皮下植入雄性Wistar大鼠（3月龄）体内。大鼠分组还接受了AT1 R拮抗剂氯沙坦或选择性α1D-AR拮抗剂BMY 7378治疗。通过尾套法测量血压；治疗2或4周后，分离血管进行功能和结构分析。血管紧张素II可升高收缩压。苯肾上腺素诱导的Ang II治疗组大鼠主动脉收缩幅度大于对照组（高40%），80 mmol/L氯化钾诱导的收缩效应与之相似。不同组间尾动脉反应无显著差异。血管紧张素II可降低α1D-ARs水平，而不改变其他α1-ARs水平，并可导致主动脉中层厚度增加（肥大），而尾动脉未发生结构变化。氯沙坦可预防和逆转高血压及肥大，而BMY 7378可预防和逆转主动脉的肥大反应，但不能预防或逆转高血压。研究结果表明，Ang II诱导的主动脉肥大反应涉及Ang II-AT1 Rs和α1D-ARs。Ang II诱导的α1D-AR介导的血管重塑独立于高血压发生。研究结果确定了一种α1D-AR介导的过程，即Ang II可独立于血压升高影响主动脉肥大。
