Additive Beneficial Effects of the Combination of a Calcium Channel Blocker and an Angiotensin Blocker on a Hypertensive Rat-Heart Failure Model

Kim‐Mitsuyama, Shokei; Izumi, Yasukatsu; Izumiya, Yasuhiro; Yoshida, Kaoru; Yoshiyama, Minoru; Itoh, Hiroshi

doi:10.1291/hypres.27.771

Cited by 33 publications

(20 citation statements)

References 24 publications

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“…Recently, it was reported that the administration of a combination therapy with ARB and CCB exerted protective effects on organs in a rodent model. 23,24 Although CCBs and ARBs are considered first-line antihypertensive drugs in Japan, the rate of attaining the target BP level by the administration of monotherapy with either drug is B12-40%. 25,26 According to a Japanese cross-sectional survey, the combination therapy with a CCB and an ARB is the most prescribed treatment for hypertensive patients in Japan.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

et al. 2009

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Benidipine, an L-and T-type calcium channel blocker, dilates both efferent and afferent arterioles and reduces glomerular pressure. Thus, it may exert renoprotective effects. We conducted an open-labeled, randomized trial to compare the blood pressure (BP)-lowering effect and antiproteinuric effect of benidipine with those of amlodipine in hypertensive patients with moderate-to-advanced-stage chronic kidney disease (CKD) (stages 3-5). These patients were already being administered the current maximum recommended doses of angiotensin receptor blockers (ARBs). Patients with BP X140/90 mm Hg, despite treatment with the maximum recommended dose of ARBs, were randomly assigned to two groups. The patients received either of the following treatment regimens: 4 mg day À1 of benidipine, which was increased up to a dose of 16 mg day À1 (B group; n¼24), and 2.5 mg day À1 of amlodipine, which was increased up to a dose of 10 mg day À1 amlodipine (A group; n¼23). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was seen in both groups. The decrease in the urinary protein to creatinine ratio in the B group was significantly lower than that in the A group. Benidipine exerted antiproteinuric effect to a greater extent than did amlodipine, even in patients with diabetic nephropathy. We conclude that the addition of benidipine, rather than amlodipine, ameliorates urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs. Therefore, we propose a combination therapy with benidipine and ARBs, even for patients with moderate-to-advanced-stage CKD.

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Section: Discussionmentioning

confidence: 99%

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

et al. 2009

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“…19,20 In short, the mouse heart was set with 10% formaldehyde overnight and embedded in paraffin. Five-mm-thick sections were cut and stained with Sirius red stain to measure the interstitial fibrosis area.…”

Section: Estimation Of Cardiac Fibrosismentioning

confidence: 99%

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

et al. 2011

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Pirfenidone (5-methyl-1-phenyl-2-[ 1 H]-pyridone) is an effective drug for idiopathic interstitial pneumonia that can prevent and reverse tissue fibrosis in several organs. Therefore, we investigated whether pirfenidone has a potential role in preventing angiotensin II (Ang II)-induced cardiac hypertrophy. A cardiac hypertrophic mouse model was created using an Ang II infusion (200 ng kg À1 min À1 ) in wild-type mice for 2 weeks. Mice were divided into the following three groups: a saline-infused (control) group, an Ang II infusion (vehicle) group and an Ang II infusion+pirfenidone-treated (PFD) group, which received pirfenidone (300 mg kg À1 per day) by gastric gavage during the Ang II infusion. At 2 weeks, we assessed hemodynamics and cardiac function and investigated tissue fibrosis of the myocardium histologically and genetically. Blood pressure in the vehicle group was significantly increased compared to the control group. Although blood pressure was not different between the vehicle and PFD groups, heart weight was significantly decreased in the PFD group. Echocardiography revealed that left ventricular hypertrophy was significantly increased in the vehicle group vs. the control group. Interestingly, pirfenidone significantly inhibited this effect. Continuous infusion of Ang II increased the perivascular and interstitial tissue fibrosis, and pirfenidone inhibited these fibrotic changes. Pirfenidone also inhibited Ang II-induced hypertrophy. In the vehicle group, the mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide and transforming growth factor-b1 were increased, which was significantly inhibited by pirfenidone. Furthermore, the expression of mineralocorticoid receptors was attenuated by pirfenidone. These results indicate that pirfenidone might be effective as an antifibrotic drug in the treatment of cardiac hypertrophy induced by hypertension.

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“…However, AZ may also reduce oxidative stress induced by some other pathway, because its effects were still observed in angiotensin II type 1 (AT1) receptor knock-out mice ( 11 ). Furthermore, combined administration of AZ with a RAS inhibitor elicited more potent renal protective activity than either agent alone in hypertensive rats complicated with heart failure ( 13 ). From these results, concomitant use of AZ plus a RAS inhibitor is expected to be more effective than use of either agent alone.…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy with Renin-Angiotensin System Inhibitors and the Calcium Channel Blocker Azelnidipine Decreases Plasma Inflammatory Markers and Urinary Oxidative Stress Markers in Patients with Diabetic Nephropathy

Ogawa¹,

Mori²,

Nako³

et al. 2008

Hypertens Res

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Additive Beneficial Effects of the Combination of a Calcium Channel Blocker and an Angiotensin Blocker on a Hypertensive Rat-Heart Failure Model

Cited by 33 publications

References 24 publications

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice

Combination Therapy with Renin-Angiotensin System Inhibitors and the Calcium Channel Blocker Azelnidipine Decreases Plasma Inflammatory Markers and Urinary Oxidative Stress Markers in Patients with Diabetic Nephropathy

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