Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats

Abstract

Background and purpose: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties.

Experimental approach: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature.

Key results: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats.

Conclusions and implications: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.

Figure 1

Ascending aortic flow (a), LV pressure (b) and ventricular and arterial P_es–SV relationships (c). (b) The dotted line represents the isovolumic pressure curve at an end-diastolic volume, which is estimated by fitting a sinusoidal function to the isovolumic portions of the measured LV pressure (Sunagawa et al., 1980). (c) Drawing a tangential line from P_isomax to the right corner of the pressure-ejected volume loop yields a point referred to as the end-systolic equilibrium point. The dotted line connecting P_isomax to the end-systolic equilibrium point constructs the ventricular P_es–SV relationship that has the slope of E_es and the volume intercept of V_eed. On the other hand, the arterial P_es–SV relationship is the dashed line connecting the end-diastolic point to the end-systolic equilibrium point, with the slope of E_a. FF, fructose-feed rats; AG, aminoguanidine.

Figure 2

Effects of fructose and AG on the chamber properties of the arterial system and the left ventricle. E_a (c) and E_es (f) represented the elastic chamber properties of the arterial system and the left ventricle, respectively. E_a can be determined by the ratio of P_es to SV. On the other hand, E_es can be calculated from the ratio of P_isomax to V_eed (see Methods). AG, aminoguanidine; FF, fructose-feeding rats; NC, normal controls.

Figure 3

Effects of fructose and AG on the matching condition for the left ventricle coupled to the arterial system. Q_load can be determined by the ratio of E_a to E_es. AG, aminoguanidine; FF, fructose-feeding rats; NC, normal controls.