Higher Ca²⁺ -sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity.

AIM:During early post-natal development, arterial contraction depends less on Ca²⁺ -signalling pathways but more on changes in Ca²⁺ -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca²⁺ -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca²⁺ -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, Ca²⁺ -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 [Ca²⁺ ]_i and Ca²⁺ -sensitivity. In contrast, in 1-week-old rats these contractions were accompanied only by an increase in Ca²⁺ -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 Thr⁸⁵⁵ 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 Ca²⁺ -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.

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