Rationale: α-calcitonin gene related peptide (αCGRP), one of the strongest vasodilators, is cardioprotective in hypertension by reducing the elevated blood pressure (BP).Objective: However, we hypothesize that endogenous, physical activity-induced αCGRP has BP-independent cardioprotective effects in chronic hypertension. MMethods and Results: Chronically hypertensive (one-kidney-one-clip surgery) WT and αCGRP-/- sedentary or voluntary wheel running mice were treated with vehicle, αCGRP, or the αCGRP receptor antagonist CGRP8-37. Cardiac function and myocardial phenotype were evaluated echocardiographically and by molecular, cellular and histological analysis, respectively. BP was similar among all hypertensive experimental groups. Endogenous αCGRP limited pathological remodeling and heart failure in sedentary, chronically hypertensive WT mice. In these mice, voluntary wheel running significantly improved myocardial phenotype and function, which was abolished by CGRP8-37 treatment. In αCGRP-/- mice, αCGRP treatment, in contrast to voluntary wheel running, improved myocardial phenotype and function. Specific inhibition of proliferation and myofibroblast differentiation of primary, murine cardiac fibroblasts by αCGRP suggests involvement of these cells in αCGRP-dependent blunting of pathological cardiac remodeling.Conclusions: Endogenous, physical activity-induced αCGRP has BP-independent cardioprotective effects and is crucial for maintaining cardiac function in chronic hypertension. Consequently, inhibiting endogenous αCGRP signaling, as currently approved for migraine prophylaxis, could endanger hypertensive patients.

中文翻译：

---

内源性，体育活动诱导的αCGRP（与降钙素基因相关的肽）在慢性高血压小鼠中的血压正常化依赖性心脏保护作用。

原理： α降钙素基因相关肽（αCGRP）是最强的血管扩张剂之一，它通过降低血压（BP）对高血压具有心脏保护作用。目的：然而，我们假设内源性体育锻炼诱导的αCGRP对慢性高血压具有BP依赖性的心脏保护作用。M方法和结果：用媒介物，αCGRP或αCGRP受体拮抗剂CGRP8-37治疗慢性高血压（单肾一夹子手术）的WT和αCGRP//久坐或自愿轮转小鼠。通过超声心动图以及通过分子，细胞和组织学分析分别评估心脏功能和心肌表型。在所有高血压实验组中，BP相似。内源性αCGRP限制了久坐的慢性高血压野生型小鼠的病理重塑和心力衰竭。在这些小鼠中，自愿轮转显着改善了心肌的表型和功能，这被CGRP8-37治疗所废除。在αCGRP-/-小鼠中，与自动轮转相比，αCGRP治疗可改善心肌的表型和功能。特异性抑制原发性肝癌的增殖和成肌纤维细胞分化结论：内源性体育锻炼诱导的αCGRP具有非BP依赖性的心脏保护作用，对于维持慢性高血压的心脏功能至关重要。因此，目前批准用于预防偏头痛的抑制内源性αCGRP信号传导可能危及高血压患者。