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Published on: October 18, 2018
Anti-inflammatory properties of azelnidipine, a dihydropyridine-based calcium channel blocker
Hiroshi Komoda1, Teruo Inoue, Koichi Node
1Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
Insights
Azelnidipine, an anti-hypertensive drug, demonstrates significant anti-inflammatory effects in patients and healthy volunteers. These actions occur independently of blood pressure reduction, suggesting novel therapeutic potential for atherosclerosis management.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Inflammation Biology
Background:
- Inflammation and oxidative stress are key drivers of atherosclerosis.
- Anti-hypertensive drugs are being investigated for anti-atherosclerotic properties beyond blood pressure control.
- Azelnidipine, a dihydropyridine calcium channel blocker, exhibits known anti-oxidative effects.
Purpose of the Study:
- To investigate the potential anti-inflammatory effects of azelnidipine.
- To determine if azelnidipine's anti-inflammatory actions are independent of its blood pressure-lowering effects.
Main Methods:
- In vivo study: 16 high-risk hypertensive patients received 16mg/day azelnidipine for 4 weeks, measuring inflammatory markers (hsCRP, IL-6, IL-8) and oxidative stress (8-OHdG).
- In vitro study: Human mononuclear leukocytes from healthy volunteers were treated with azelnidipine (100 nM) to assess inhibition of IL-8 production induced by fMLP.
- Assessed changes in serum and urinary markers, and leukocyte inflammatory responses.
Main Results:
- In hypertensive patients, azelnidipine treatment significantly reduced serum hsCRP, IL-6, IL-8, and urinary 8-OHdG levels without altering blood pressure.
- In vitro, azelnidipine significantly inhibited fMLP-induced IL-8 production in human leukocytes.
- Observed anti-inflammatory effects in leukocytes, which lack voltage-operated calcium channels, suggest a non-L-type calcium channel mechanism.
Conclusions:
- Azelnidipine possesses significant anti-inflammatory properties.
- These anti-inflammatory effects are independent of azelnidipine's anti-hypertensive action.
- Azelnidipine may offer therapeutic benefits in managing atherosclerosis through mechanisms beyond calcium channel blockade.
Abstract:
Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect.
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