Abstract| Volume 23, ISSUE 10, SUPPLEMENT , S14, October 2017

Lack of Glucagon Promotes Cardiac Remodeling and Hypertension in Mice via Elevation of Norepinephrine

      Background: Glucagon (Gcg) maintains blood glucose level to the physiological extent in response to various pathophysiological conditions. Previous studies suggest that Gcg promotes chronotropic and inotropic effects on heart; however, current understanding regarding the cardiovascular impact of Gcg remains quite limited. In the present study, by use of Gcg-null mice, we aimed to seek for the pathophysiological role(s) of Gcg on cardiac function and remodeling. Methods and Results: Gcg-null mice [18 week-old male Gcg-enhanced green fluorescent protein (EGFP) knock-in mice] exhibited marked left ventricular dilatation [in mm; LVDd/Ds 3.9/2.9 (Gcg-null) and 3.6/2.1 (wild)] and consequent reduction in left-ventricular systolic function [(LVFS; 27.2% (Gcg-null) and 42.5% (wild)). Their left ventricular wall thick remained normal range and electron microscopy revealed the decline in mitochondrial count in Gcg-null heart. Gcg-null mice exhibited hypertension and cardiac catheterization consistently revealed elevation of arterial blood pressure and diastolic dysfunction [dp/dtmin, Tau, and left ventricular maximum pressure (Pmax)]. Picrosirius red staining revealed that enhanced perivascular fibrosis in Gcg null heart. Interestingly, the circulating angiotensin-II concentration was decreased; however, the norepinephrine level of Gcg-null mice was more than 3 fold higher than wild type counterpart. Conclusions: The present study revealed the possible link between Gcg and sympathetic nerve activity which modulates cardiac remodeling and blood pressure, implicating a novel pathophysiological pathway that contributes to development of heart failure.
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