Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

Abstract

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

“…A variety of other classes of drugs are also effective in limiting TNF-α production, beyond the direct neutralization activity of TNF-α blockers. ACE inhibitors are used in the treatment of kidney diseases to limit hypertensive renal injury, with much interest surrounding the immunomodulatory activity of captopril [ 151 ]. An in vivo experiment involving spontaneously hypertensive rats (SHR) demonstrated that higher mRNA and protein expression of inflammatory cytokines, such as TNF-α and IL-6, could be attenuated by captopril treatment [ 151 ].…”

“…ACE inhibitors are used in the treatment of kidney diseases to limit hypertensive renal injury, with much interest surrounding the immunomodulatory activity of captopril [ 151 ]. An in vivo experiment involving spontaneously hypertensive rats (SHR) demonstrated that higher mRNA and protein expression of inflammatory cytokines, such as TNF-α and IL-6, could be attenuated by captopril treatment [ 151 ]. Further, the group also observed higher phosphorylation of NF-κB and associated activation kinases in SHR than in controls, which could be suppressed by captopril treatment [ 151 ].…”

“…An in vivo experiment involving spontaneously hypertensive rats (SHR) demonstrated that higher mRNA and protein expression of inflammatory cytokines, such as TNF-α and IL-6, could be attenuated by captopril treatment [ 151 ]. Further, the group also observed higher phosphorylation of NF-κB and associated activation kinases in SHR than in controls, which could be suppressed by captopril treatment [ 151 ]. This demonstrates that the renoprotective effects of captopril may take place not only through lowering of blood pressure, but through modulation of pro-inflammatory gene transcription via NF-κB [ 151 ].…”

The Role of Cystatin C and Albumin in the Differential Diagnosis of Primary Chronic Glomerulonephritis and Hypertension-Induced Renal Injury

“…Primary chronic glomerulonephritis (PCG) is one of major causes of end-stage renal disease (ESRD) among chronic renal disease patients in China [1][2][3]. Hypertension-induced renal injury (HRI) generally occurs during the middle and late stages of hypertension and has become an important public health problem [4][5]. Both of them are typically characterized by proteinuria, hematuria, hypertension, renal inflammation and so on, which makes it difficult to clinically diagnose PCG and HRI.…”

Heart Protection by Herb Formula BanXia BaiZhu TianMa Decoction in Spontaneously Hypertensive Rats

“…It is noteworthy that the impact of risk factors applies especially to early-stage arterial hypertension, for which inflammation has been highlighted [7, 8]. Proinflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 (IL-1), tumour necrosis factor (TNF- α ), and inducible nitric oxide synthase (iNOS), are critical to the onset of inflammation and are known to activate the nuclear factor NF-κB pathway [9]. Thus, therapeutic interventions to reduce activation of inflammatory cascade may prove beneficial for reducing end-organ damage and preventing the consequences of hypertension, including myocardial infarction and heart failure [10].…”