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

• Published in: Acta Physiologica Vol. 223; no. 3; p. e13044
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England 01-07-2018
• Subjects: Rho-kinase; smooth muscle; maturation; protein kinase C; MYPT1; small arteries
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/apha.13044

During early post-natal development, arterial contraction depends less on Ca
-signalling pathways but more on changes in Ca
-sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca
-sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca
-sensitivity of contraction in intact arteries of 1-week-old rats.
We studied 1-week-old, 4- to 5-week-old and 10- to 12-week-old rats performing isometric myography, Ca
-fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia.
In 10- to 12-week-old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca
]
and Ca
-sensitivity. In contrast, in 1-week-old rats these contractions were accompanied only by an increase in Ca
-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
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.
Our results suggest that the higher Ca
-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.