Laboratory of Diabetes and Exercise Metabolism, Departmentof Physiology, MidwesternUniversity, AZ 85308, USA.
Acta Physiol (Oxf). 2010 Oct;200(2):147-58. doi: 10.1111/j.1748-1716.2010.02134.x.
pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1β, IL-6 and tumour necrosis factor-α in the hypertrophied RV in a model of PH.
RV hypertrophy was induced in male Sprague-Dawley rats with monocrotaline (MCT; 60 mg kg(-1) ) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio.
in the RV of MCT-treated rats, a approximately 40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1β and IL-6.
our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1β and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH.
大鼠肺动脉高压（PH）可导致右心室（RV）肥大、炎症和血浆及 RV 中利钠肽（NP）水平升高。由于催产素受体（OTR）的释放一氧化氮（NO）和心房利钠肽（ANP）的功能，我们研究了 PH 对 OTROTR、NP（A、心房；B、脑）和受体（NPRs）、一氧化氮合酶（NOS）、白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α在 PH 模型中 RV 肥大中的基因和蛋白表达的影响。
雄性 Sprague-Dawley 大鼠用单克隆毒素（MCT；60mgkg(-1)）诱导 RV 肥大，并通过 RV 重量增加和 RV-[左心室（LV）和室间隔]比增加来确认。
与对照大鼠的 RV 相比，MCT 处理大鼠的 RV 中 OTRmRNA 和蛋白约减少 40%。这种减少与两个心室中 ANP 和 BNP 的转录物增加以及 A、B 和 C 型 NP 受体 mRNA 表达的相应增加有关。RV 中诱导型 NOS 蛋白表达增加，而内皮型 NOS 转录物仅在 MCT 处理大鼠的 LV 中增加。在 MCT 处理大鼠的 RV 中，OTR 的下调也与 IL-1β 和 IL-6 的 mRNA 表达增加有关。
我们的结果表明，MCT 处理大鼠 RV 中 OTR 的下调与 NP 及其受体以及 IL-1β 和 IL-6 的表达增加有关。RV 心肌中 OTR 的这种减少可能对 MCT 诱导的 PH 模型中的心脏功能产生影响。
