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The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin

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Abstract

Background

Uterotonic mediators: endothelin-1 (ET-1), arginine vasopressin (AVP), and nitric oxide (NO) play important roles in the regulation of uterine contractility. We hypothesize that NO affects both ET-1 or AVP. Therefore, this study investigated the involvement of extended exogenous NO release in the regulation of responses of the human non-pregnant myometrium to ET-1 and AVP.

Methods

Specimens were obtained from 10 premenopausal women, undergoing hysterectomy for benign gynecological disorders. Responses of the myometrial strips to ET-1 or AVP in the absence and presence of an exogenous NO donor (diethylenetriamine; DETA/NO; 10−4 mol/L) were recorded under isometric conditions. To inhibit endogenous NO, a competitive inhibitor of NO synthase, L-NG-nitroarginine (L-NNA) was added to the organ bath.

Results

ET-1 enhanced the spontaneous contractile activity of the myometrium more powerfully (p s< 0.01) than AVP. Preincubation with exogenous NO weakened ET-1- or AVP-induced increases in this contractile activity (p s< 0.05). However, unexpected results were obtained after preincubation with L-NNA and with DETA/NO then added. Both ET-1 and AVP induced augmented contractile effects in almost all concentrations compared with the responses to these peptides alone or after NOS synthase inhibition (both p s< 0.01).

Conclusions

This study demonstrated for the first time that extended incubation with a NO donor influences the uterine muscle response evoked by ET-1 and AVP. Both endogenous and exogenous NO is involved in the control of the uterine responses to ET-1 or AVP of non-pregnant myometrium. Furthermore, both peptides stimulate increased uterine contractility when the local imbalance between the constrictive and relaxing mediators takes place.

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Abbreviations

AUC:

area-under-the-curve

AVP:

arginine vasopressin

cGMP:

cyclic guanosine monophosphate

DETA/NO:

diethylenetriamine

ET-1:

endothelin-1

KCa2+:

calcium-dependent potassium

L-NMA:

N-nitro-L-arginine-methyl-ester

L-NNA:

L-NG-nitroarginine

NO:

nitric oxide

NOS:

NO synthase

cNOS:

constitutive NOS

eNOS NOS3:

endothelial NOS

sGC:

guanylyl cyclase

SR:

sarcoplasmic reticulum

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Authors and Affiliations

  1. Department of Biophysics, Medical University of Bialystok, Bialystok, Poland

    Beata Modzelewska, Marzena Tylicka & Tomasz Kleszczewski

  2. Department of Gynecology and Gynecologic Oncology, Medical University of Bialystok, Bialystok, Poland

    Maciej Jóźwik

  3. Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland

    Marcin Jóźwik

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  1. Beata Modzelewska
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  2. Maciej Jóźwik
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Correspondence to Beata Modzelewska.

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Modzelewska, B., Jóźwik, M., Jóźwik, M. et al. The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin. Pharmacol. Rep 71, 892–898 (2019). https://doi.org/10.1016/j.pharep.2019.05.003

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  • DOI: https://doi.org/10.1016/j.pharep.2019.05.003

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