Differential β₁ Cardiac Adrenoceptor Modulation of Nitric Oxide Isoforms by β₁ IgG from Patients with Periodontitis during Short-Term Hypoxia

Sabrina Ganzinelli, Enri Borda

Pharmacology Unit, School of Dentistry, University of Buenos Aires and Argentine National Research Council (CONICET), Buenos Aires, Argentina.

DOI: 10.4236/pp.2015.612057                

Abstract

Background: We demonstrated previously that serum IgG from periodontitis patients interacting with the second extracellular loop of the human cardiac β₁ adrenoreceptors triggers the production of second messengers. In this paper we quantified the production of nitrates/nitrites and nitric oxide (NO), which in turn induces nitric oxide synthase (NOS) mRNA expression. Methods: We determined using β₁ IgG, NOS activity isoforms, NOS expression, nitrate/nitrite assay, cGMP accumulation and PKC activity. Results: We established that serum β₁ IgG autoantibodies and NO might be considered as early markers in normoxia/hypoxia system in rat isolated atria. The β₁ IgG autoantibodies from periodontitis patients, while stimulating myocardial atria β₁ adrenoreceptors, exert an increase on NO levels indirectly quantified as nitrite/nitrate, which acts as NO-storage molecules with significant increase in neuronal NOS (nNOS) and inducible NOS (iNOS) mRNA levels in hypoxia conditions. The significant increase in nNOS/iNOS mRNA and NOS activity as well as in NO levels after short-time hypoxia in rat isolated atria was detected. The expression of these genes are related with the increase in atria dF/dt, cyclic GMP (cGMP) and protein kinase C (PKC) activity and resemble the results obtained by Isoproterenol, an β₁ adrenoreceptor agonist. Conclusion: These findings indicate that short-term hypoxia up-regulated rat atria NO/NOS system in the presence of β₁ IgG autoantibodies shows that an antibody interacting with rat atria β₁ adrenoreceptor can act as expression inducer of proinflammatory NO and its metabolites and that it might be useful and helps to maintain heart function and to prevent necrosis and subsequent loss of heart function during hypoxia.

Keywords

Nitric Oxide Synthase, Nitric Oxide, Hypoxia, Normoxia, Autoantibody

Conflicts of Interest

The authors declare no conflicts of interest.

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