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Higher Ca 2+ ‐sensitivity of arterial contraction in 1‐week‐old rats is due to a greater Rho‐kinase activity
Author(s) -
Mochalov S. V.,
Tarasova N. V.,
Kudryashova T. V.,
Gaynullina D. K.,
Kalenchuk V. U.,
Borovik A. S.,
Vorotnikov A. V.,
Tarasova O. S.,
Schubert R.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13044
Subject(s) - rho associated protein kinase , fasudil , vasoconstriction , methoxamine , contraction (grammar) , rho kinase inhibitor , myograph , isometric exercise , medicine , endocrinology , electrical impedance myography , contractility , muscle contraction , kinase , chemistry , vasodilation , receptor , biochemistry , agonist
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 MYPT 1 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.