Functional and Histological Changes in Umbilical Artery and Myometrium Isolated from IUGR Complicated Pregnancies.

Objective: To investigate the relaxation responses mediated by L-type Ca2+ channels and big-conductance Ca2+-activated K+ (BKCa) channels and histological changes in the human umbilical artery (HUA) and myometrium smooth muscle isolated from pregnancies complicated with intrauterine growth restriction (IUGR).Methods: The muscle reactivity and the histology of the smooth muscle of the HUA and myometrium retrieved from 14 women with IUGR and 14 controls were investigated by the isolated tissue bath and immunohistochemical method.Results: In HUA, the maximum relaxation responses and pD2 values of nifedipine and NS11021 (BKCa channel opener) were significantly increased and significant histopathological changes are observed in the IUGR group.Conclusions: The pathogenesis of IUGR might be associated with the impairment in the functional responses of L-type Ca2+ channels and BKCa channels in HUA smooth muscle. The increased staining of myometrium and UC with HIF-1α in IUGR may indicate apoptosis, histological damage, and impaired fetal growth.

In vitro effect of hyoscine-N-butyl bromide and diclofenac sodium in human tuba uterina.

INTRODUCTION: To investigate the in vitro effect of diclofenac on tubal smooth muscle as an alternative to hyoscine-N-butyl bromide, which is used for premedication before hysterosalpingography (HSG). MATERIAL AND METHODS: Fallopian tubes were retrieved from seven healthy women after bilateral tubal ligation and in vitro contractility and histological studies were conducted using tissue bath and immunohistochemistry. RESULTS: Diclofenac sodium and hyoscine-N-butyl bromide did not significantly change the basal mean tension; however, they decreased the contractions induced by potassium chloride (KCl). The relaxant effect of diclofenac sodium and hyoscine-N-butyl bromide was not statistically significantly different. The presence of cyclooxygenase (COX)-2 enzyme in the fallopian tube was demonstrated by immunohistochemical studies. CONCLUSIONS: The in vitro relaxant effect of diclofenac sodium on the fallopian tube is similar to hyoscine-N-butyl bromide. Diclofenac may have the potential to be used as an alternative to hyoscine-N-butyl bromide in premedication in HSG.

Comparison of relaxant effects of nifedipine and NS11021 on isolated umbilical arteries of healthy and preeclamptic pregnant women.

OBJECTIVES: Potassium (K+) channel openers and calcium (Ca2+) channel blockers are currently used to treat acute severe hypertension in pregnancy. We aimed to investigate the vasorelaxant effect of NS11021, a potent and specific big-conductance Ca2+-activated K+ (BKCa) channel activator, and to compare it with the vasorelaxant effect of nifedipine on human umbilical arteries (HUAs) isolated from healthy and preeclamptic pregnants. STUDY DESIGN: A total of 29 HUAs were isolated immediately after delivery from 14 healthy and 15 preeclamptic pregnant with severe features. The concentration-dependent relaxation responses were obtained to nifedipine and NS11021 on HUAs precontracted with endothelin-1 (ET-1) (10-8 M) in an isolated tissue bath. RESULTS: Both nifedipine and NS11021 caused concentration-dependent relaxation responses in HUAs from healthy and preeclamptic pregnants. While the maximum responses (Emax) and pD2 values of nifedipine did not change significantly in both groups, the Emax and pD2 values of NS11021 were significantly decreased in the preeclampsia group (Emax ± SEM; %75.57 ± 4.53 and %43.75 ± 14.00 and pD2 ± SEM; 6.92 ± 0.26 and 5.24 ± 0.53 respectively, p < 0.05). In addition, the pD2 value of NS11021 was not significantly different from that of nifedipine in the control group, but decreased significantly in the preeclampsia group (pD2 ± SEM 7.1 ± 0.41 and 5.2 ± 0.53, p < 0.05, respectively). CONCLUSIONS: Efficacy and potency of NS11021 decreased in HUAs from preeclamptic pregnants. Also, NS11021 is less potent than nifedipine in the preeclampsia group. BKCa channels may have a role in the pathogenesis of preeclampsia, however, further experimental studies are needed to elucidate that.

In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions.

Relaxin, an endogenous peptide hormone, elicits vascular relaxation by its direct effect or by modulating the endothelium-dependent relaxation response and is clinically evaluated for the treatment of coronary artery disease. However, its effect on penile tissue has not been explored yet. This study aimed to investigate the effect of serelaxin, recombinant human relaxin-2, on rat corpus cavernosum (CC) under healthy and hyperglycemic conditions. Strips of CC obtained from thirty-nine male Wistar rats weighing 300-350 g were used in organ baths for isometric tension studies to investigate the serelaxin-mediated relaxation (10-12-10-7 M) under normoglycemic conditions and the effect of serelaxin on endothelium-dependent [nitric oxide (NO)- and prostacyclin-mediated] relaxation responses under hyperglycemic conditions. The in vitro hyperglycemia model was created by 3 h of incubation with 44 mM glucose monohydrate +120 µM methylglyoxal. NO-dependent relaxation responses were evaluated by cumulative acetylcholine (10-9-10-4 M) administration in the presence of indomethacin (10-6 M). Prostacyclin-mediated relaxation was evaluated by cumulative administration of iloprost (10-9-10-6 M), a prostacyclin analog. Maximum relaxation responses to serelaxin were not significantly different compared to the time-control (p = 0.480). Three hours of incubation of rat CC in hyperglycemic conditions impaired NO- and prostacyclin-mediated relaxation responses (p = 0.032 and p = 0.047, respectively). Serelaxin coincubation worsened NO-mediated relaxation responses (p = 0.016) but did not affect prostacyclin-mediated responses (p = 0.425). Together, our results demonstrate that in vitro administration of serelaxin does not cause relaxation in penile tissue and short-term in vitro serelaxin treatment in hyperglycemic conditions mimicked diabetes modulates endothelium-dependent responses by worsening NO-mediated responses. Serelaxin exerts different effects via different mechanism on endothelium-dependent responses depending on the dose and duration of exposure. Therefore, proper timing and dosing of serelaxin administration in the penile tissue need to be investigated in further studies in diabetic animal models.