Relaxing effect of a new ruthenium complex nitric oxide donor on airway smooth muscle of an experimental model of asthma in rats
NO is a potent bronchodilator and NO donor compounds have demonstrated clinical significance for obstructive airway diseases. This study evaluated the relaxation mechanisms of two NO donors, a ruthenium compound (TERPY) and sodium nitroprusside (SNP) in rat tracheas with ovalbumin induced asthma (OVA group) and in another control group. The effect of TERPY and SNP was evaluated in tracheal rings in an isolated organ chamber. The contribution of K+ channels, sGC/cGMP pathway, phosphodiesterases, and extra and intracellular Ca2+ sources were analyzed. The TERPY and SNP induced tracheal smooth muscle relaxation in both groups. However, the maximum effect induced by TERPY was higher than that of SNP in both control (110.2 3.2% vs 68.3 3.1% P 0.001) and OVA groups (106.1 1.5% vs 49.9 2.7% P 0.001) In the control group, TERPY relaxation was induced by the activation of K+ channels and reduction of the calcium influx, while in the OVA group, these same effects were also brought about by TERPY, but with participation of the sGC/cGMP pathway. In both groups, SNP induced relaxation occurred through the activation of K+ channels, sGC/cGMP pathway and reduction of calcium influx. However, the activation of sGC pathway and reticular Ca2+ ATPase seemed to be reduced in the OVA group. Furthermore, TERPY is capable of reversing the contraction of carbachol in asthmatic bronchioles. Finally, TERPY and SNP relaxation mechanisms were modified by asthma. SNP presented less relaxation than TERPY, which induced full relaxation with greater participation of K+ and Ca2+ fluxes through the membrane, thereby making TERPY a promising drug for reversing the narrowing of airways.
Clinical and experimental pharmacology physiology