Higher Ca 2+ -sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity.

Autor: Mochalov SV; Medical Faculty Mannheim, Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Heidelberg University, Mannheim, Germany.; Faculty of Biology, M.V. Lomonosov, Moscow State University, Moscow, Russia.; ChemRar Research and Development Institute, Khimki, Moscow Region, Russia., Tarasova NV; Medical Faculty Mannheim, Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Heidelberg University, Mannheim, Germany.; Faculty of Biology, M.V. Lomonosov, Moscow State University, Moscow, Russia.; Molecular Medicine Institute, I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Kudryashova TV; Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia., Gaynullina DK; Medical Faculty Mannheim, Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Heidelberg University, Mannheim, Germany.; Faculty of Biology, M.V. Lomonosov, Moscow State University, Moscow, Russia.; Department of Physiology, Russian National Research Medical University, Moscow, Russia., Kalenchuk VU; Faculty of Basic Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia., Borovik AS; State Research Center of the Russian Federation - Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Vorotnikov AV; Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.; Medical Center, M.V. Lomonosov Moscow State University, Moscow, Russia., Tarasova OS; Faculty of Biology, M.V. Lomonosov, Moscow State University, Moscow, Russia.; State Research Center of the Russian Federation - Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Schubert R; Medical Faculty Mannheim, Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Heidelberg University, Mannheim, Germany.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2018 Jul; Vol. 223 (3), pp. e13044. Date of Electronic Publication: 2018 Feb 17.
DOI: 10.1111/apha.13044
Abstrakt: Aim: During early post-natal development, arterial contraction depends less on Ca 2+ -signalling pathways but more on changes in Ca 2+ -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca 2+ -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca 2+ -sensitivity of contraction in intact arteries of 1-week-old rats.
Methods: We studied 1-week-old, 4- to 5-week-old and 10- to 12-week-old rats performing isometric myography, Ca 2+ -fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia.
Results: In 10- to 12-week-old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca 2+ ] i and Ca 2+ -sensitivity. In contrast, in 1-week-old rats these contractions were accompanied only by an increase in Ca 2+ -sensitivity. All MX-induced effects were reduced by the Rho-kinase inhibitor Y-27632; this reduction was complete only in 1-week-old rats. The Rho-kinase specific site Thr 855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1-week-old, but not 10- to 12-week-old rats; this effect was also inhibited completely by Y-27632. The Rho-kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4- to 5-week-old rats reduced it considerably in 1-week-old rats.
Conclusion: Our results suggest that the higher Ca 2+ -sensitivity of arterial contraction in 1-week-old compared to 10- to 12-week-old rats is due to a greater Rho-kinase activity. Constitutively active Rho-kinase contributes to MX-induced contraction in 10- to 12-week-old rats. In 1-week-old rats, additional Rho-kinase activation is involved. This remodelling of the Rho-kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.
(© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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