endothelin-1 and Cystitis

To determine the effect of endothelin-1 (ET-1) on the production of interleukin-6 (IL-6) in cultured human detrusor smooth muscle cells (HDSMCs) and the effect of IL-6 on the contractile response of bladder smooth muscle strips from rats.. The expression of IL-6 mRNA and production of IL-6 protein in cultured HDSMCs treated with the different concentrations of ET-1 were assayed by reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay, respectively. The strips from Sprague-Dawley rats were either untreated or treated with 1 ng/mL of IL-6 for 60 min. Using increasing cumulative concentrations of acetylcholine (ACh), bethanechol (BCh), or sodium nitroprusside, we assessed the concentration-contraction or the relaxation responses. In cystitis-induced strips, change of contractions induced by noradrenaline (NA) with or without treatment of IL-6 were assessed. The IL-6-treated strips were incubated for 30 min in the presence or absence indomethacin or SQ29548, and then the effects on ACh- or BCh-induced contractions were measured.. The expression of IL-6 mRNA and the production of IL-6 protein on the cultured HDSMCs pretreated by ET-1 were significantly higher than in the control (P<0.05). The ACh- and BCh-induced contractions were increased in the IL-6 pretreated strips from both dome and trigone, regardless of the presence of urothelium (P<0.05). The presence of cystitis augmented the NA-induced contractions (P<0.05). The contractions induced by ACh and BCh were inhibited by indomethacin and SQ29548.. ET-1 induces expression of IL-6 mRNA and production of IL-6 protein on HDSMCs. IL-6 enhances detrusor smooth muscle contractility via the muscarinic or adrenergic receptor pathway.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Cells, Cultured; Cyclooxygenase Inhibitors; Cystitis; Dose-Response Relationship, Drug; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Unsaturated; Humans; Hydrazines; Indomethacin; Interleukin-6; Muscle Contraction; Myocytes, Smooth Muscle; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Urinary Bladder

Endothelin (ET)-1 is causatively involved in ischemia-reperfusion induced acute inflammatory reactions and microcirculatory disturbances in many organs. We investigated the role of endothelin-1 in the microcirculatory consequences of ischemia-reperfusion of the bladder using intravital fluorescence videomicroscopy.. Male Sprague-Dawley rats were used in the experiments. The animals were randomly assigned to a sham operated group or to 1 of 2 ischemia-reperfusion groups that underwent 60 minutes of ischemia followed by 30 minutes of bladder reperfusion. In 1 ischemia-reperfusion group the animals were pretreated with BQ 610, a specific ET-A receptor blocker. The bladder was placed on an especially designed stage for intravital fluorescence videomicroscopy measurements. Venular red blood cell velocity, functional capillary density, venular and arteriolar diameter, venular and arteriolar macromolecular leakage, and leukocyte-endothelial cell interactions in postcapillary venules were determined using a computer assisted analyzing system.. Functional capillary density, red blood cell velocity, venular and arteriolar diameter were significantly decreased and macromolecular leakage was significantly enhanced after bladder ischemia-reperfusion. The number of rolling and adherent leukocytes was significantly increased in postcapillary venules. Pretreatment with BQ 610 was effective for attenuating the effects of ischemia-reperfusion induced inflammation but could not completely prevent microcirculatory failure.. Ischemia-reperfusion induced cystitis leads to significant impairment of the microcirculation and ET-1 is suggested to have an important role in this process. Pretreatment with an ET-A receptor antagonist reduces ischemia-reperfusion related microvascular disturbances in the bladder.

Topics: Acute Disease; Animals; Cystitis; Endothelin Receptor Antagonists; Endothelin-1; Male; Microcirculation; Oligopeptides; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Reperfusion Injury; Urinary Bladder