endothelin-1 and Peritoneal-Diseases

Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain.. Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1β and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1β and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited.. The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1β induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1β and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist.. The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain.. The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain.

Topics: Animals; Behavior, Animal; Bradykinin; Bradykinin B2 Receptor Antagonists; Case-Control Studies; Cells, Cultured; Culture Media, Conditioned; Cyst Fluid; Endometriosis; Endothelin-1; Female; Humans; Interleukin-1beta; Mice; Ovarian Diseases; Pain; Peritoneal Diseases; Receptors, Bradykinin; RNA, Messenger; Stromal Cells

The current study was planned to investigate intestinal blood flow alterations and the role of ET-1 receptor blockade in the formation of postoperative intraperitoneal adhesion formation.. Twenty-eight adult Wistar Albino rats weighing between 250 g and 300 g were divided into four groups. Control group (group 1; n=7) did not undergo any operation. Sham group (group 2; n=7) had only laparotomy. In the adhesion group (group 3; n=7), peritoneal patch (1x1 cm) excision from the right abdominal wall and cecal abrasion were done as "adhesion model operation". One week following this, treatment group (group 4; n=7) received a non-selective ET-1 receptor blocking agent bosentan (30 mg/kg, IP) intra-abdominally, once a day for four days. Intestinal blood flow through the superior mesenteric artery was measured, on postoperative seventh day. Adhesion severity and extension as well as myeloperoxidase activity in the adhesion were calculated.. Mean intestinal blood flow significantly increased in adhesion group (81.9+/-5.6 ml/100 g) when compared to group 1 (65.5+/-1.2 ml/100 g). Bosentan caused a significant decrease (44.3+/-6.9 ml/100 g) in intestinal blood flow when compared to group 1 and group 2. Sham group (62.2+/-1 ml/100 g) had similar blood flow level with the control group (65.5+/-1.2 ml/100 g). Adhesion scores were similar in adhesion and Bosentan groups. Sham group had almost no adhesions. Myeloperoxidase activity in adhesion tissue was significantly higher in bosentan group.. Non-selective ET-1 receptor blockade has no effect on prevention of the formation of intra-abdominal adhesion, but causes a decrease in intestinal blood flow. Adhesion formation increases intestinal blood flow. Adhesion formation is accompanied by increased polymorphonuclear infiltration despite bosentan treatment.

Topics: Abdomen; Animals; Antihypertensive Agents; Blood Flow Velocity; Bosentan; Disease Models, Animal; Endothelin-1; Intestines; Mesenteric Arteries; Peritoneal Diseases; Postoperative Complications; Pulsatile Flow; Rats; Rats, Wistar; Sulfonamides; Tissue Adhesions