Abstract
BackgroundRenal artery stenosis (RAS) promotes hypertension and cardiac dysfunction. The 2-kidney, 1-clip mouse model in many ways resembles RAS in humans and is amenable for genetic manipulation, but difficult to evaluate noninvasively. We hypothesized that cardiovascular magnetic resonance (CMR) is capable of detecting progressive cardiac and renal dysfunction in mice with RAS and monitoring the progression of the disease longitudinally.MethodsRAS was induced at baseline in eighteen mice by constricting the renal artery. Nine additional animals served as normal controls. CMR scans (16.4 T) were performed in all mice one week before and 2 and 4 weeks after baseline. Renal volumes and hemodynamics were assessed using 3D fast imaging with steady-state precession and arterial spin labelling, and cardiac function using CMR cine. Renal hypoxia was investigated using blood oxygen-level dependent (BOLD) MR.ResultsTwo weeks after surgery, mean arterial pressure was elevated in RAS mice. The stenotic kidney (STK) showed atrophy, while the contra-lateral kidney (CLK) showed hypertrophy. Renal blood flow (RBF) and cortical oxygenation level declined in the STK but remained unchanged in CLK. Moreover, cardiac end-diastolic and stroke volumes decreased and myocardial mass increased. At 4 weeks, STK RBF remained declined and the STK cortex and medulla showed development of hypoxia. Additionally, BOLD detected a mild hypoxia in CLK cortex. Cardiac end-diastolic and stroke volumes remained reduced and left ventricular hypertrophy worsened. Left ventricular filling velocities (E/A) indicated progression of cardiac dysfunction towards restrictive filling.ConclusionsCMR detected longitudinal progression of cardiac and renal dysfunction in 2K, 1C mice. These observations support the use of high-field CMR to obtain useful information regarding chronic cardiac and renal dysfunction in small animals.
Highlights
Renal artery stenosis (RAS) promotes hypertension and cardiac dysfunction
Cardiovascular disease (CVD) associated with renovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD) [1,2,3]
Renal volume and function Two weeks after inducing RAS, the stenotic kidney (STK) cortical and medullary volumes significantly decreased, and by the fourth week were on average reduced to 39% and 61% of their baseline values, respectively (p < 0.001)
Summary
Renal artery stenosis (RAS) promotes hypertension and cardiac dysfunction. We hypothesized that cardiovascular magnetic resonance (CMR) is capable of detecting progressive cardiac and renal dysfunction in mice with RAS and monitoring the progression of the disease longitudinally. Renal artery stenosis (RAS) is associated with renin-angiotensin system driven hypertension, which initiates a cascade of biological events including mechanical larger size of their renal artery, which facilitates the surgical procedure, in recent years this model has been developed in mice, mainly due to the possibility of combining this procedure with genetic manipulations [11,12,13]. Cardiovascular magnetic resonance (CMR) is able to evaluate renal volume and hemodynamics [17,18,19]. Renal hypoxia is an important marker of progressive kidney dysfunction and contributes to development of hypertension [22]
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