The present study aimed to test whether angiotensin receptor blockers (ARBs) are cardioprotective after myocardial infarction (MI) by preventing augmented local renin-angiotensin-system (RAS)-induced oxidative stress injury and senescence, preserving resident stem cells, and restoring the insulin-like growth factor (IGF-1)/IGF-1 receptor (IGF-R) pathway. Sprague-Dawley rats with ligated or unligated coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Heart function and molecular and histological changes were assessed. It was found MI induced left ventricular dysfunction and remodeling, increased levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine and cell senescence marker p16ink4a, and downregulated the IGF-1/IGF-1R/Akt pathway after both 3 and 9 weeks post-MI. MI induced an increase in stem cells identified by immunostaining for c-kit and Wilms' tumor-1 predominantly after 3 weeks. Losartan significantly inhibited local cardiac RAS activation and improved left ventricular function and remodeling at both timepoints. Losartan also preserved c-kit- and Wilms' tumor-1-positive cells (particularly at 3 weeks), attenuated 8-hydroxy-2'-deoxyguanosine- and p16ink4a-positive cardiomyocytes, and restored the IGF-1/IGF-1R/Akt pathway at both 3 and 9 weeks. In conclusion, ARBs aided cardiac repair post-MI through short-term preservation of stem cells and persistent anti-oxidative stress and anti-senescence effects, partially by attenuating activation of cardiac RAS and restoring the local IGF-1/IGF-1R/Akt pathway.

To compare the long-term efficacy of corticosteroids (P) alone or in combination with cyclophosphamide (CTX), leflunomide (LEF), or Angiotensin-convertase inhibitors or angiotensin II receptor blockers (ACEI/ARB) in treatment for IgA nephropathy (IgAN), 311 patients with IgAN were identified. Therapeutic effectiveness (including progression, partial remission, complete remission) and combined renal endpoint (defined as 30% reduction in eGFR or ESRD) were compared based on different therapies. After immunosuppressive and ACEI/ARB treatment, the levels of eGFR, proteinuria and albumin were significantly improved at the last follow-up, the extent of improvement of eGFR, proteinuria, and albumin was more notable in P + CTX group and P + LEF group. 41%, 52.2%, 55.3% and 55.2% in P + CTX, P + LEF, P and ACEI/ARB group achieved complete remission, respectively. Multivariate regression analysis indicated that only proteinuria (Relative risk (RR) 0.82(0.72-0.94), P = 0.004) and tubular atrophy/interstitial fibrosis (RR 0.26(0.13-0.57), P = 0.001) were predictors for complete remission. The optimal cutoffs of eGFR was 47.085 ml/min/1.73 m2 predicting renal function recovery in P + CTX therapy. In conclusion, tubular atrophy/interstitial fibrosis and massive proteinuria were poor predictors for complete remission in IgAN, it appears as though patients may have benefited from immunosuppressive treatment but that comparison to a well-matched contemporary control group or, ideally, a randomized controlled clinical trial, would be required to show this.

Multiple clinical trials have demonstrated that renin-angiotensin system (RAS) blockade with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers effectively reduces chronic kidney disease (CKD) progression. However, most clinical trials excluded participants with advanced CKD (ie, estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged that initiation of RAS blockade is often associated with an acute reduction in eGFR, which is thought to be functional, but may result in long-term preservation of kidney function through the reductions in glomerular intracapillary pressure conferred by these agents. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies regarding use of RAS blockade in patients with advanced kidney disease. We review available published data on this topic and provide perspective on the impact of RAS blockade on changes in eGFRs and potassium levels. We conclude that more research is needed to evaluate the therapeutic index of RAS blockade in patients with advanced CKD.

Inflammation is a normal part of the immune response to injury or infection but its dysregulation promotes the development of inflammatory diseases, which cause considerable human suffering. Nonsteroidal anti-inflammatory agents are the most commonly prescribed agents for the treatment of inflammatory diseases, but they are accompanied by a broad range of side effects, including gastrointestinal and cardiovascular events. The renin-angiotensin system (RAS) is traditionally known for its role in blood pressure regulation. However, there is increasing evidence that RAS signaling is also involved in the inflammatory response associated with several disease states. Angiotensin II increases blood pressure by binding to angiotensin type 1 (AT1 ) receptor, and direct renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) are clinically used as antihypertensive agents. Recent data suggest that these drugs also have anti-inflammatory effects. Therefore, this review summarizes these recent findings for the efficacy of two of the most widely used antihypertensive drug classes, ACE inhibitors and ARBs, to reduce or treat inflammatory diseases such as atherosclerosis, arthritis, steatohepatitis, colitis, pancreatitis, and nephritis.