Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure

Abstract

Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Centrally acting drug moxonidine decreases reactive oxygen species via inactivation of the phosphoinositide-3 kinase signaling in the rostral ventrolateral medulla in hypertensive rats

“…In our preliminary experiments, central infusion of yohimbine or efaroxan alone had little effect on basal BP and ROS generation in the RVLM (data not shown). As reported previously [3,30], we also confirmed that central injection of moxonidine significantly decreased BP and excretion of uNE. In this work, moxonidine reduced ROS content in a dose-dependent manner, indicating a specificity of effects of moxonidine.…”

“…An enhanced oxidation in the RVLM via activation of phosphoinositide-3 kinase (PI3K) signal pathway has been suggested to lead to the neurogenic hypertension [15]. Recently, it is reported that moxonidine attenuates the whole brain oxidative stress in rats with hypertensive heart failure [3]. Therefore, the goal of this study was to determine whether central antihypertensive mechanism of moxonidine is associated with anitoxidative stress in the RVLM and possible mechanism involved.…”

“…INTRODUCTION I t has been documented that the centrally acting antihypertensive drug moxonidine activates I 1 -imidazoline receptor (I 1 R) and/or a 2 -adrenoceptor (a 2 AR) within the rostral ventrolateral medulla (RVLM) to lower blood pressure (BP) and sympathetic outflow [1][2][3]. However, the central antihypertensive mechanism is not fully understood.…”

Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor

“…Three sections were examined per heart using a four times magnified lens for the fibrosis analysis (Honda et al. 2013). A calibrated digital camera (Model BZ-9000, Keyence Co., Osaka, Japan) and an imaging analysis program (BZH1C; Keyence Co., Tokyo, Japan) were used in the histological analysis.…”

Activation of imidazoline I1 receptor by moxonidine regulates the progression of liver fibrosis in the Nrf2-dependent pathway

“…Treatment of hypertensive rats with MOX can reduce left ventricular IL-1b, TNF-a and IL-6 levels, as well as inhibit inducible nitric oxide synthase (iNOS) expression through Akt and p38 MAPK signaling pathways [26]. What's more, MOX can attenuate noradrenaline-induced cardiomyocyte apoptosis and fibroblast proliferation, and thus restrain myocardial fibrosis and ventricular remodeling [27]. These results suggested that MOX might be a potential anti-inflammatory and anti-fibrotic agent.…”