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Antioxidant and antiinflammatory effect of carvedilol in mononuclear cells of hypertensive patients

      To the Editor:
      Yasunary et al
      • Yasunari K.
      • Maeda K.
      • Nakamura M.
      • et al.
      Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.
      have recently reported that carvedilol treatment decreased oxidative stress and C-reactive protein level in mononuclear cells from essential hypertensive patients compared with propranolol, even though the decrease in mean arterial pressure was similar. Given the known relation between cardiovascular risk and oxidative stress, inflammation, and C-reactive protein, the authors suggested that carvedilol may have anti-inflammatory effects, possibly by decreasing oxidative stress in mononuclear cells.
      • Yasunari K.
      • Maeda K.
      • Nakamura M.
      • et al.
      Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.
      We would like to point out that we have provided further evidence of carvedilol’s antioxidant and antiinflammatory effect based on the results of our study examining carvedilol’s effect on cyclosporin-induced post-transplant hypertension.
      • Calò L.
      • Giacon B.
      • Davis P.A.
      • et al.
      Oxidative stress and TGFβ in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.
      Hypertension is a common finding during treatment with calcineurin inhibitors such as cyclosporin and tacrolimus, as they are powerful stimulators of oxidative stress, which leads to hypertension and its long-term complication, such as cardiovascular remodeling and atherogenesis through nitric oxide degradation, endothelial dysfunction, and increased production of transforming growth factor β (TGFβ).
      • Paul L.C.
      Chronic allograft nephropathy an update.
      We reported that carvedilol treatment decreased blood pressure and oxidative stress markers, such as plasma levels of nitrotyrosine, an extimate of peroxynitrite, and mononuclear cell TGFβ mRNA production. In addition, carvedilol treatment increased both plasma antioxidant power and mononuclear cell heme oxygenase-1 mRNA production in these patients.
      • Calò L.
      • Giacon B.
      • Davis P.A.
      • et al.
      Oxidative stress and TGFβ in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.
      These changes are potentially important, as TGFβ is a major profibrotic cytokine
      • Basile D.P.
      The transforming growth factor β system in kidney disease and repair recent progress and future directions.
      and heme oxygenase-1 is protective against oxidative stress and possesses long-term anti-inflammatory and antiproliferative effects.
      • Maines M.D.
      The heme oxygenase system:a regulator of second messenger gases.
      • Nath K.A.
      • Vercellotti G.M.
      • Grande J.P.
      • et al.
      Heme protein-induced chronic renal inflammation suppressive effect of induced heme oxygenase-1.
      Finally, the carvedilol-induced reduction of peroxynitrite level suggests that nitric oxide bioavailability increased.
      In conclusion, the results of our study in mononuclear cells of post-transplant hypertensive patients,
      • Calò L.
      • Giacon B.
      • Davis P.A.
      • et al.
      Oxidative stress and TGFβ in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.
      when combined with those reported by Yasunari et al,
      • Yasunari K.
      • Maeda K.
      • Nakamura M.
      • et al.
      Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.
      provide substantial evidence for the antioxidant and anti-inflammatory effects of carvedilol. Not only do these studies provide cellular mechanisms for the effects noted, they also indicate that carvedilol provides protection against hypertension as well as oxidative stress, which plays pivotal roles in endothelial dysfunction, fibrogenesis, and cardiovascular remodeling.

      References

        • Yasunari K.
        • Maeda K.
        • Nakamura M.
        • et al.
        Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.
        Am J Med. 2004; 116: 460-465
        • Calò L.
        • Giacon B.
        • Davis P.A.
        • et al.
        Oxidative stress and TGFβ in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.
        Clin Nephrol. 2002; 56: 103-110
        • Paul L.C.
        Chronic allograft nephropathy.
        Kidney Int. 1999; 56: 783-793
        • Basile D.P.
        The transforming growth factor β system in kidney disease and repair.
        Curr Opin Nephrol Hypertens. 1999; 81999: 21-30
        • Maines M.D.
        The heme oxygenase system:a regulator of second messenger gases.
        Annu Rev Pharmacol Toxicol. 1997; 37: 517-554
        • Nath K.A.
        • Vercellotti G.M.
        • Grande J.P.
        • et al.
        Heme protein-induced chronic renal inflammation.
        Kidney Int. 2001; 59: 106-117