Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT1 Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice

Rafiq, Kazi; Sherajee, Shamshad J.; Hitomi, Hirofumi; Nakano, Daisuke; Kobori, Hiroyuki; Ohmori, Koji; Mori, Hideki; Kobara, Hideki; Masaki, Tsutomu; Kohno, Masakazu; Nishiyama, Akira

doi:10.1371/journal.pone.0082082

Cited by 6 publications

(10 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, a recent study showed that ARB plus CCB has beneficial effects against cerebrovascular-renal injury in type 2 diabetic mice [18]. Consistent with previous studies [19], [30], the present study showed that in DSS rats, 4 weeks of treatment with HS diet caused hypertension, proteinuria, glomerular and tubulointerstitial damage.…”

Section: Discussionsupporting

confidence: 92%

“…Gene expression in renal cortical tissue was analyzed by RT-PCR using a LightCycler FastStart DNA Master SYBR Green I kit and an ABI Prism 7000 Sequence Detection System (Applied Biosystems, Foster City, USA) as described previously [18] , [23] . The oligonucleotide primer sequences for rat β-actin, TGF-β 1 , α-SMA, type 1 collagen, MCP-1, PAI-1, gp91phox, Nox-1, E-cadherin, and fibroblast-specific protein 1 (FSP-1) are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

“…Thus, it is possible that continuous suppression of the renin-angiotensin system (RAS) can not only prevent, but also restore renal tissue injury. In this regard, recent experimental and clinical studies highlighted the potential beneficial effects of combination therapy with an ARB and calcium channel blocker (CCB) [13] – [18] . However, the renoprotective effect of dietary salt reduction with combined ARB plus CCB therapy during the development of salt-dependent hypertension has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regression of Glomerular and Tubulointerstitial Injuries by Dietary Salt Reduction with Combination Therapy of Angiotensin II Receptor Blocker and Calcium Channel Blocker in Dahl Salt-Sensitive Rats

et al. 2014

Self Cite

View full text Add to dashboard Cite

A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB) plus calcium channel blocker (CCB) reverses renal tissue injury in Dahl salt-sensitive (DSS) hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl) for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl), NS + an ARB (olmesartan, 10 mg/kg/day), NS + a CCB (azelnidipine, 3 mg/kg/day), NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day). Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regression of Glomerular and Tubulointerstitial Injuries by Dietary Salt Reduction with Combination Therapy of Angiotensin II Receptor Blocker and Calcium Channel Blocker in Dahl Salt-Sensitive Rats

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…High blood pressure is a risk factor for diabetic nephropathy [27,28]. In previous reports, olmesartan inhibited albuminuria in diabetic animals, but this effect was not tightly correlated with blood pressure control [16,17,20,29]. Of course, we cannot exclude that the reduced blood pressure by olmesartan treatment contributed to the decreased albuminuria in db/db mice, however the focus of our study was to investigate the effect of olmesartan on angiotensin II/SIRT1 pathway triggered podocyte apoptosis.…”

Section: Discussionmentioning

confidence: 86%

Olmesartan Prevents Microalbuminuria in db/db Diabetic Mice Through Inhibition of Angiotensin II/p38/SIRT1-Induced Podocyte Apoptosis

Yang

et al. 2016

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Blockage of the renin-angiotensin II system (RAS) prevents or delays albuminuria in diabetic patients. The aim of this study was to investigate the inhibitory mechanism of the angiotensin receptor blocker olmesartan on albuminuria in a murine model of diabetic nephropathy. Methods: Male db/db diabetic mice were fed with placebo or 20 mg/kg olmesartan by daily gavage for 12 weeks. Conditionally immortalized mouse podocytes were treated with glucose, angiotensin II, olmesartan or p38 inhibitor s8307 in different experimental conditions after differentiation. Results: Olmesartan reduced albuminuria in db/db mice without change in body weight and glycemia. The increase of apoptotic cells and decrease of podocytes in the diabetic glomerulus were prevented by olmesartan. Moreover, olmesartan restored silent mating type information regulation 1 (SIRT1) expression in diabetic glomeruli. Furthermore, olmesartan treatment suppressed p38 phosphorylation but did not restore adenosine 5‘-monophosphate-activated protein kinase (AMPK) phosphorylation in the diabetic glomerulus. In vitro study revealed that olmesartan prevented angiotensin II/p38/SIRT1 induced podocyte apoptosis, but it only slightly prevented high glucose/AMPK/SIRT1 induced podocyte apoptosis. In addition, the p38 inhibitor s8307 reversed SIRT1 expression and angiotensin II induced podocyte apoptosis. Conclusions: Olmesartan reduced albuminuria in diabetic nephropathy through inhibiting angiotensin II/p38/SIRT1 triggered podocyte apoptosis.

show abstract

“…The combination therapy of ARBs plus CCBs was reported to be more effective than monotherapy (Ogawa et al, ). In fact, olmesartan plus azelnidipine enhanced cerebrovascular and renal protective effects by suppressing NADPH oxidase‐dependent oxidative stress (Rafiq et al, ) and showed antiatherogenic effects by suppressing oxidative stress and activating endothelial nitric oxide synthase (Noda et al, ). In a clinical study for type 2 diabetic hypertensive patients, the combination of olmesartan plus azelnidipine was more beneficial against BP morning surge, showed a greater decrease in heart rate, and improved glucose tolerance and microalbuminuria more than candesartan plus amlodipine therapy (Daikuhara et al, ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke‐prone spontaneously hypertensive rats

Omote

Deguchi

Kono

et al. 2014

J of Neuroscience Research

View full text Add to dashboard Cite

An angiotensin 2 type 1 receptor blocker, olmesartan, and a calcium channel blocker, azelnidipine, possess not only an antihypertensive effect but also an antioxidative effect and other beneficial effects. In the present study, we examined the efficacy of olmesartan and azelnidipine monotherapy (2 mg/kg or 10 mg/kg each) and their combination therapy (1 mg/kg each) on stroke-prone spontaneously hypertensive rats (SHR-SP) in relation to oxidative stress, inflammation, and the neurovascular unit. In comparison with the vehicle group, body weight, regional cerebral blood flow, and motor function were preserved, whereas systolic blood pressure and diastolic blood pressure decreased in the five drug-treatment groups. Spontaneous infarct volume decreased with the low-dose combination of olmesartan plus azelnidipine and with the high-dose olmesartan, with a further decrease in the high-dose azelnidipine group. In addition, these drugs dose-dependently reduced oxidative stresses, proinflammatory molecules, and well-preserved components of the neurovascular unit. The low-dose combination of olmesartan plus azelnidipine showed a better effect than the low-dose olmesartan or azelnidipine monotherapy. The present study shows that the low-dose combination of olmesartan plus azelnidipine demonstrates a greater synergistic benefit than monotherapy with a low-dose of olmesartan or azelnidipine in SHR-SP for preventing spontaneous infarct volume, reducing oxidative stresses and proinflammatory molecules, and imparting neurovascular protection. In addition, a high-dose of olmesartan showed a greater benefit without the lowering of blood pressure, probably because of the antioxidative and anti-inflammatory effects. A high dose of azelnidipine showed the best benefit, probably because of the two effects mentioned above related to the lowering of blood pressure.

show abstract

Calcium Channel Blocker Enhances Beneficial Effects of an Angiotensin II AT1 Receptor Blocker against Cerebrovascular-Renal Injury in type 2 Diabetic Mice

Cited by 6 publications

References 50 publications

Regression of Glomerular and Tubulointerstitial Injuries by Dietary Salt Reduction with Combination Therapy of Angiotensin II Receptor Blocker and Calcium Channel Blocker in Dahl Salt-Sensitive Rats

Regression of Glomerular and Tubulointerstitial Injuries by Dietary Salt Reduction with Combination Therapy of Angiotensin II Receptor Blocker and Calcium Channel Blocker in Dahl Salt-Sensitive Rats

Olmesartan Prevents Microalbuminuria in db/db Diabetic Mice Through Inhibition of Angiotensin II/p38/SIRT1-Induced Podocyte Apoptosis

Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke‐prone spontaneously hypertensive rats

Contact Info

Product

Resources

About