Effect of carvedilol on reactive oxygen species and enzymes linking innate and adaptive immunity.

Objectives: Neutrophils and macrophages are critical components of our innate host defenses. They are a potential source of nitric oxide (NO) and superoxide, known to play an important role in many physiological processes including defense, immune and inflammatory responses. Myeloperoxidase (MPO), a major NO scavenger and a marker of oxidative stress, as well as increased inducible nitric oxide synthase (iNOS) expression, may affect the NO-superoxide balance, critical for cellular redox balance in the cardiovascular system at physiologic conditions.

On the pharmacology and toxicology of neutrophils.

Objectives: To study the effect of H1-antihistamines dithiaden (Dit) and loratadine (Lor) and compare it with that of histamine (His) on phorbolmyristate acetate (PMA) stimulated chemiluminescence (CL) of whole blood, isolated neutrophils, release of myeloperoxidase (MPO), and on superoxide (SO) generation.

Methods: Luminol- and isoluminol-enhanced CL was applied for measuring the oxidative burst, spectrophotometry was used for determination of MPO (o-dianisidine) and SO generation (superoxide dismutase inhibition of cytochrome c).

Results: Dit and Lor dose-dependently inhibited CL of whole blood and significantly decreased oxidative burst both at the extra- and intracellular sites of neutrophils.

Extra- and intracellular formation of reactive oxygen species by human neutrophils in the presence of pheniramine, chlorpheniramine and brompheniramine.

Background: Allergic inflammation was found to be accompanied by activation of neutrophils. Since this resulted in increased formation of reactive oxygen species, the antioxidative activity of antiallergic drugs was considered to decrease the risk of tissue damage. However, if the drug-induced inhibition of radical formation occurred intracellularly, it could disturb regulation of neutrophil functions and decrease bactericidal activity of these cells.

On the antioxidant activity of carvedilol in human polymorphonuclear leukocytes in vitro and ex vivo.

Objectives: In the present study we investigated whether the beta-adrenoceptor antagonist carvedilol (CARV) [Dilatrend] prevented reactive oxygen metabolite (ROM) production in human polymorphonuclear leukocytes (PMNL) or interfered with ROM already generated. To specify the site of action of CARV, we evaluated its effect on extra- and intracellular ROM generation. In addition, we studied the effect of CARV therapy on ROM production in whole blood obtained from patients with congestive heart failure (CHF) combined with type II diabetes mellitus.