NADPH oxidase derived ROS promote arterial contraction in early postnatal rats by activation of L-type voltage-gated Ca2+ channels

Shvetsova, A.A.; Shateeva, V.S.; Khlystova, M.A.; Makukha, Y.A.; Tarasova, O.S.; Gaynullina, D.K.

Авторы: Shvetsova Anastasia A., Shateeva Valentina S., Khlystova Margarita A., Makukha Yulia A., Tarasova Olga S., Gaynullina Dina K.
Журнал: Free Radical Research
Том: 59
Номер: 1
Год издания: 2025
Издательство: Taylor & Francis
Местоположение издательства: United Kingdom
Первая страница: 49
Последняя страница: 60
DOI: 10.1080/10715762.2024.2448483
Аннотация: Reactive oxygen species (ROS) produced by NADPH oxidase promote contraction of peripheral arteries, which is especially pronounced in early postnatal period in comparison to adulthood, butthe mechanisms of such vasomotor influence are poorly understood. We tested the hypothesis that Rho-kinase and protein kinase C (PKC) mediate procontractile influence of NADPH oxidase derived ROS in peripheral artery of early postnatal rats. In addition, we evaluated the involvement Src-kinase and L-type voltage-gated Ca2+ channels (LTCC ) into procontractile influence of ROS,produced by NADPH oxidase, because of their known interplay with Rho-kinase and PKC pathways.Saphenous arteries from 11- to 15-day-old male rats were studied using quantitative PCR, isometric myography and lucigenin-enhanced chemiluminescence. Arterial tissue of early postnatal rats contained Nox2, Nox4, Duox1 and Duox2 mRNAs, among which Nox2 mRNA was the mostabundant. Pan-NADPH oxidase inhibitor VAS2870 (10 μM) significantly reduced arterial contractileresponses to methoxamine. The inhibitors of Rho-kinase (Y27632, 3 μM), PKC (GF109203X, 10 μM)and Src-kinase (PP2, 10 μM), as well as LTCC blockers (nimodipine, 0.1 μM, and verapamil, 0.1 μM) also reduced methoxamine-induced contraction. Importantly, the effect of VAS2870 persisted inthe presence of Rho-kinase, PKC or Src-kinase inhibitors, but not in the presence of LTCC blocker. Notably, the blockade of LTCC did not affect either basal or NADPH-induced O2 •− production. Our data show that LTCC , but not Rho-kinase, PKC or Src-kinase are involved into procontractile effect of ROS, produced by NADPH oxidase, in saphenous artery of young rats. Сalcium influx through LTCC does not activate ROS production by NADPH oxidase.
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NADPH oxidase derived ROS promote arterial contraction in early postnatal rats by activation of L-type voltage-gated Ca2+ channelsстатья Исследовательская статья

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