INTRODUCTION: Cyclic guanosine monophosphate (cGMP) levels can be regulated by heme oxygenase-1 and 2 (HO-1 and HO-2)-derived carbon monoxide (CO). AIMS: Assessment of the effect of upregulating CO in rat corpora cavernosa (CC) on cavernous cGMP. METHODS: Three experimental groups were studied: first group (N = 40), short-term HO induction over 2 weeks by injection of intraperitoneal increasing doses of hemin; the second group (N = 40) was subjected to intracavernosal injection of CO donor, CORM-3, or its inactive form (iCORM-3) over 2 weeks; the third group (N = 60) was subdivided into three subgroups: the first one received a combined hemin and CORM-3, the second one received hemin and its inhibitor stannus mesoporphyrin (SnMP), and third one received a combined hemin, CORM-3, and SnMP. MAIN OUTCOME MEASURES: In CC, HO-1 and HO-2 gene expression, Northern blot and Western blot, cGMP levels, and HO enzyme activity. RESULTS: In the first group, maximum induction of HO-1 gene expression, HO enzyme activity, and cGMP occurred with 4-mg hemin dose with a successive increase over 2 weeks. In the second group, CORM-3 increased cGMP by twofold compared with iCORM-3, and also increased HO-1 protein. In the third group, SnMP inhibited the enhancing effect of CORM-3 and HO on erectile signaling molecules; i.e., HO-1 gene, enzyme activity, and cGMP. CONCLUSIONS: CORM-3- or hemin-mediated CO release could increase cavernous tissue cGMP.
INTRODUCTION:Cyclic guanosine monophosphate (cGMP) levels can be regulated by heme oxygenase-1 and 2 (HO-1 and HO-2)-derived carbon monoxide (CO). AIMS: Assessment of the effect of upregulating CO in rat corpora cavernosa (CC) on cavernous cGMP. METHODS: Three experimental groups were studied: first group (N = 40), short-term HO induction over 2 weeks by injection of intraperitoneal increasing doses of hemin; the second group (N = 40) was subjected to intracavernosal injection of COdonor, CORM-3, or its inactive form (iCORM-3) over 2 weeks; the third group (N = 60) was subdivided into three subgroups: the first one received a combined hemin and CORM-3, the second one received hemin and its inhibitor stannus mesoporphyrin (SnMP), and third one received a combined hemin, CORM-3, and SnMP. MAIN OUTCOME MEASURES: In CC, HO-1 and HO-2 gene expression, Northern blot and Western blot, cGMP levels, and HO enzyme activity. RESULTS: In the first group, maximum induction of HO-1 gene expression, HO enzyme activity, and cGMP occurred with 4-mg hemin dose with a successive increase over 2 weeks. In the second group, CORM-3 increased cGMP by twofold compared with iCORM-3, and also increased HO-1 protein. In the third group, SnMP inhibited the enhancing effect of CORM-3 and HO on erectile signaling molecules; i.e., HO-1 gene, enzyme activity, and cGMP. CONCLUSIONS: CORM-3- or hemin-mediated CO release could increase cavernous tissue cGMP.
Authors: Mohamed T Abdel aziz; Mohamed F El Asmar; Hazem M Atta; Soheir Mahfouz; Hanan H Fouad; Nagwa K Roshdy; Laila A Rashed; Dina Sabry; Amira A Hassouna; Fatma M Taha Journal: J Exp Clin Cancer Res Date: 2011-05-05