title: Soluble guanylate cyclase redox state under oxidative stress conditions in isolated monkey coronary arteries.
abstract: Coronary artery disease is associated with oxidative stress due to the excessive generation of free radicals in the vascular wall. This study investigated the impact of tert-butyl hydroperoxide (t-BuOOH), a peroxyl radical generator, on the redox state of soluble guanylate cyclase (sGC) in isolated monkey coronary arteries. Helically cut strips of endothelium-intact monkey coronary arteries treated with the nitric oxide synthase inhibitor NG-nitro-L-arginine (10μmol/L) were exposed for approximately 60 min to either no drug or t-BuOOH (100μmol/L) in the presence and absence ofα-tocopherol (300μmol/L). Relaxation and cGMP levels in response to the sGC stimulator BAY 41-2272 and the sGC activator BAY 60-2770 were assessed by organ chamber technique and enzyme immunoassay, respectively. The relaxant response to BAY 41-2272 was significantly impaired by the exposure to t-BuOOH, whereas the response to BAY 60-2770 was significantly augmented. In addition, vascular cGMP accumulation caused by BAY 41-2272 was decreased by the exposure to t-BuOOH, whereas for BAY 60-2770, it was increased. These effects of t-BuOOH were abolished by coincubation withα-tocopherol. Furthermore, correlations were observed between BAY compound-induced relaxant magnitudes and cGMP levels. Therefore, it is concluded that increased oxidative stress leads to disruption of the sGC redox state in monkey coronary arteries. This finding is of great importance for understanding coronary physiology in primates.
authors.affiliation: Department of Pharmacology Shiga University of Medical Science Otsu Shiga Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tawa
authors.affiliation: Department of Pharmacology Shiga University of Medical Science Otsu Shiga Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Okamura
keywords: Coronary artery; oxidative stress; redox state; sGC activator; sGC stimulator; soluble guanylate cyclase