Mechanisms of Sodium Hypochlorite-Induced Contraction of Rat Aorta: Potential Importance in Atherogenesis and Apoptotic Phenomena in Cardiovascular Diseases

The present study was designed to investigate the effects of sodium hypochlorite (NaOCl) on isolated rat aortic rings with and without endothelium. In the absence of any vasoactive agent, NaOCl alone elicited an endothelium-independent contraction in rat aortic rings in a concentration-dependent manner. NaOCl-induced contractions of intact rat aortic rings appeared, however, to be slightly stronger than those on denuded rat aortic rings. Our results demonstrate a stronger contractile effect of NaOCl on aortic segments of rats with increasing age and weight. The contractile responses to NaOCl were neither reversible nor reproducible in the same ring; even small concentrations of NaOCl resulted in tachyphylaxis. Removal of extracellular calcium ions (Ca2+) or buffering intracellular Ca2+ with 10 μM acetyl methyl ester of bis (o-aminophenoxy) ethane-N,N,N′,N′,-tetraacetic acid (BAPTA-AM) significantly attenuated the contractile actions of NaOCl. The presence of 1 μM staurosporine, 1 μM bisindolylmaleimide I, 1 μM Gö697{12-(2-Cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo{2,3-a] pyrrolo {3,4-c} carbazole, inhibitors of protein kinase C (PKC), 2 μM PD-098059 {2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one, inhibitor of extracellular signal-regulated kinases)}, 10 μM genistein (inhibitor of tyrosine kinase), and 1 μM wortmannin {an antagonist of phosphatidylinositol 3-kinases (PI3Ks)} completely inhibited the contractions induced by NaOCl. Several specific antagonists of possible endogenously- formed vasoconstrictors did not inhibit or attenuate NaOCl-induced contractions. Our new results suggest that NaOCl-triggered contractions on rat aortic rings are Ca2+-dependent. Several intracellular signal transduction systems seem to play roles in NaOCl-induced vasoconstriction of rat aortic rings.

Author(s): Jian-Ping Liu, Wenyan Li, Bella T Altura, and Burton M Altura

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