Renal Damage after Myocardial Infarction Is Prevented by Renin-Angiotensin-Aldosterone-System Intervention

Abstract

Recently, it was shown that myocardial infarction aggravates preexistent mild renal damage that is elicited by unilateral nephrectomy in rats. The mechanism behind this cardiorenal interaction likely involves the renin-angiotensin-aldosteronesystem and/or vasoactive peptides that are metabolized by neutral endopeptidase (NEP). The renoprotective effect of angiotensin-converting enzyme inhibition (ACEi) as well as combined ACE/NEP inhibition with a vasopeptidase inhibitor (VPI) was investigated in the same model to clarify the underlying mechanism. At week 17 after sequential induction of unilateral nephrectomy and myocardial infarction, treatment with lisinopril (ACEi), AVE7688 (VPI), or vehicle was initiated for 6 wk. Proteinuria and systolic BP (SBP) were evaluated weekly. Renal damage was assessed primarily by proteinuria, interstitial ␣-smooth muscle actin (␣-SMA) staining, and the incidence of focal glomerulosclerosis (FGS). At start of treatment, proteinuria had increased progressively to 167 ؎ 20 mg/d in the entire cohort (n ‫؍‬ 42). Both ACEi and VPI provided a similar reduction in proteinuria, ␣-SMA, and FGS compared with vehicle at week 23 (proteinuria 76 ؎ 6 versus 77 ؎ 4%; ␣-SMA 60 ؎ 6 versus 77 ؎ 3%; FGS 52 ؎ 14 versus 61 ؎ 10%). Similar reductions in systolic BP were observed in both ACEi-and VPI-treated groups (33 ؎ 3 and 37 ؎ 2%, respectively). Compared with ACEi, VPI-treated rats displayed a significantly larger reduction of plasma (41 ؎ 5 versus 61 ؎ 4%) and renal (53 ؎ 6 versus 74 ؎ 4%) ACE activity. It is concluded that both ACEi and VPI intervention prevent renal damage in a rat model of cardiorenal interaction. VPI treatment seemed to provide no additional renoprotection compared with sole ACEi after 6 wk of treatment in this model, despite a more pronounced ACE-inhibiting effect of VPI.

Angiotensin II Receptor Blocker Attenuates Intrarenal Renin-Angiotensin-System and Podocyte Injury in Rats with Myocardial Infarction

“…The pathophysiology in cardiorenal syndrome is poorly understood and likely involves interrelated concepts such as low cardiac output, increased venous congestion and renal venous pressure, neurohormonal and inflammatory activation, and local changes [2,19]. In good agreement with other observations [1,8,9], the present study has shown that common renal damage after MI could be significantly prevented by RAS intervention, such as with the use of losartan. Furthermore, increased inflammatory cell infiltration and fibrosis within the kidneys occurring post-MI heart failure has also been demonstrated by our previous study [6] and the other study [10].…”

Renal Sympathetic Denervation Suppresses De Novo Podocyte Injury and Albuminuria in Rats With Aortic Regurgitation

“…Here, we have proposed a concept that ties our results together with those of previous studies 56, 57 . Chronic cardiac volume overload leads to SNS activation, resulting in augmentation of intrarenal RAS and NADPH oxidase-dependent ROS production.…”

Activation of renal angiotensin type 1 receptor contributes to the pathogenesis of progressive renal injury in a rat model of chronic cardiorenal syndrome

“…Subsequently, based on results obtained using an ACE inhibitor, they suggested that the RAS was involved in the pathogenesis of the progressive renal injury (54). In that study, however, the ACE inhibitor caused a dramatic decrease in blood pressure and an improvement in cardiac parameters.…”