Sakima Atsushi, Averill David B, Gallagher Patricia E, Kasper Sherry O, Tommasi Ellen N, Ferrario Carlos M, Diz Debra I
The Hypertension and Vascular Disease Center, Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
Hypertension. 2005 Aug;46(2):333-40. doi: 10.1161/01.HYP.0000178157.70142.33. Epub 2005 Jul 11.
Age-related baroreflex reductions in function may originate from central neural dysregulation as well as vascular structural/functional changes. We determined the role of 2 angiotensin (Ang) peptides at the nucleus tractus solitarii in age-related baroreflex impairment. Baroreflex sensitivity control of heart rate in response to increases in blood pressure was tested in younger (3 to 5 months) and older (16 to 20 months) anesthetized male Sprague-Dawley rats before and after bilateral solitary tract injections of the Ang II type 1 (AT1) receptor antagonist candesartan (24 pmol) or the Ang-(1-7) antagonist (D-Ala7)-Ang-(1-7) (144 fmol or 24 pmol). Basal reflex sensitivity of older rats was significantly lower than younger rats. In younger rats, the reflex was facilitated by bilateral candesartan injections and attenuated by bilateral (D-Ala7)-Ang-(1-7) injections. In older rats, the reflex was facilitated by AT1 blockade; however, (D-Ala7)-Ang-(1-7) injected into the solitary tract nucleus had no effect. Neprilysin mRNA in the medulla was lower in older rats compared with younger rats, whereas angiotensin-converting enzyme (ACE), ACE2, and mas receptor mRNA levels of older rats did not differ from values of younger rats. Thus, opposing actions of endogenous Ang II and Ang-(1-7) in the solitary tract nucleus contribute to baroreflex function in response to increases in mean arterial pressure of younger rats. The attenuated counterbalancing effect of Ang-(1-7) on baroreflex function is lost in older rats, which may be attributable to diminished production of the peptide from neprilysin.
与年龄相关的压力感受器反射功能减退可能源于中枢神经调节异常以及血管结构/功能改变。我们确定了两种血管紧张素（Ang）肽在孤束核中对与年龄相关的压力感受器反射损害的作用。在双侧孤束注射血管紧张素II 1型（AT1）受体拮抗剂坎地沙坦（24皮摩尔）或血管紧张素 -（1 - 7）拮抗剂（D - Ala7）- 血管紧张素 -（1 - 7）（144飞摩尔或24皮摩尔）之前和之后，对年轻（3至5个月）和老年（16至20个月）麻醉的雄性Sprague - Dawley大鼠进行血压升高时心率的压力感受器反射敏感性控制测试。老年大鼠的基础反射敏感性显著低于年轻大鼠。在年轻大鼠中，双侧注射坎地沙坦可促进反射，而双侧注射（D - Ala7）- 血管紧张素 -（1 - 7）则减弱反射。在老年大鼠中，AT1阻断可促进反射；然而，注入孤束核的（D - Ala7）- 血管紧张素 -（1 - 7）没有效果。与年轻大鼠相比，老年大鼠延髓中的中性内肽酶mRNA较低，而老年大鼠的血管紧张素转换酶（ACE）、ACE2和mas受体mRNA水平与年轻大鼠的值没有差异。因此，内源性血管紧张素II和血管紧张素 -（1 - 7）在孤束核中的相反作用有助于年轻大鼠对平均动脉压升高的压力感受器反射功能。血管紧张素 -（1 - 7）对压力感受器反射功能的减弱的平衡作用在老年大鼠中丧失，这可能归因于中性内肽酶产生的该肽减少。
