Anti-spasmolytic effects of BAY 60-2770, a soluble guanylate cyclase activator, in isolated coronary arteries

Abstract

This study investigated whether soluble guanylate cyclase (sGC) activators (activating the heme-oxidized and heme-free sGC) have potential as therapeutic drugs for coronary artery spasm. Isolated canine and porcine coronary arteries were suspended in organ chambers for isometric tension recording. The contractile responses of canine coronary arteries to potassium chloride (3×10-2 M), endothelin-1 (3×10-11 to 3×10-8 M), prostaglandin F2α (10-8 to 10-5 M), and 5-hydroxytryptamine (10-9 to 10-6 M) were suppressed by previous exposure to the sGC activator BAY 60-2770 (10-10, 10-9 and 10-8 M). In porcine coronary arteries, the addition of BAY 60-2770 (10-10, 10-9 and 10-8 M) concentration-dependently prolonged the cycle length of 3,4-diaminopyridine (10-2 M)-induced phasic contractions and reduced the peak tension. As for vessel-size-dependent difference in vasoreactivity, BAY 60-2770 (10-12 to 10-7 M) caused a greater relaxation of porcine coronary arteries precontracted with endothelin-1 (3×10-8 M) in small arteries (#9 in AHA classification) than in large arteries (#6 in AHA classification). These findings suggest that sGC activators are beneficial for the treatment of vasospastic angina. In addition, anti-spasmolytic efficacy of sGC activators may be expected to be observed even in microvascular angina.