Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function

Abstract

Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5–10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e′) (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction.

Mechanisms Involving Ang II and MAPK/ERK1/2 Signaling Pathways Underlie Cardiac and Renal Alterations during Chronic Undernutrition

“…It has been demonstrated that RAS is important in the pathological heart hypertrophy [49], [50] that is counteracted by blocking AT 1 R [51] with simultaneous prevention of cardiac electric remodeling [52]. The view that kidney receptors are associated with heart receptors in the cardiac structural and electric remodeling receives further support from the observation that elimination of AT 1 R in mice reduces cardiac hypertrophy and the risk of hypertension [49], and also from the observation that primary renal dysfunction in rats is associated with an augmented risk of congestive cardiac failure in simultaneous alterations that constitute a cardiorenal syndrome [53].…”

Dissecting the genetic predisposition to albuminuria and endothelial dysfunction in a genetic rat model

“…Moreover, previous studies indicated that a multifactorial process leads to albuminuria to which multiple genetic loci are also contributing [8][9][10][11][12][13]. In addition, previous studies in MWF demonstrated an impaired endothelium-dependent relaxation in coronary microvessels [7] or aortas [16,17]. In this regard the Munich Wistar Frömter (MWF) rat model appears of interest to shed new light on this question.…”

Agkistrodon acutus-purified protein C activator protects human umbilical vein endothelial cells against H2O2-induced apoptosis

“…Recent studies indicated that VEC injury could be caused by many substances: ox-LDL, Hcy, AngII, TNF-a and oxidative stress. VEC malfunction plays very important role in the pathogenesis of atherosclerosis, hypertension and diabetes (Falskov et al 2011;Szymanski et al 2012). Thus, the protection of VEC can prevent and treat several diseases.…”