RHO
Hypertension is characterized by abnormal vascular contractility and function.
Arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats develop
spontaneous tone that is not observed in arteries from normotensive rats.
Inhibition of phosphoinositide 3-kinase (PI3-kinase) by LY294002 reduces
spontaneous tone development. The Rho/Rho-kinase pathway has been suggested to
play a role in hypertension and may be dependent on PI3-kinase activity. We
hypothesized that Rho-kinase is involved in spontaneous tone development and
that Rho/Rho-kinase is a downstream effector of PI3-kinase. Using endothelium-denuded
aortic strips in isolated tissue bath, we demonstrated that Y27632 (1 micro M),
a Rho-kinase inhibitor, significantly reduced spontaneous tone in the DOCA
aorta, but did not affect sham aorta basal tone (DOCA:63.5 +/- 15.9 vs. Sham:1.2
+/- 0.4 Total change % phenylephrine contraction). We examined the interaction
between the PI3-kinase and Rho pathways by observing the effects of LY294002 on
a Rho-kinase effector, myosin phosphatase (MYPT), and Y27632 on a PI3-kinase
effector, Akt, using Western blot analysis. Inhibition of PI3-kinase reduced
spontaneous tone, but had no effect on the phosphorylation status of MYPT,
indicating that PI3-kinase is not a downstream effector of Rho/Rho-kinase.
These data indicate that there is little interaction between the Rho/Rho-kinase
and PI3-kinase pathways in the DOCA-salt aorta, and the two pathways appear to
operate in parallel in supporting spontaneous arterial tone. These data reflect
spontaneous tone only and do not rule out the possibility of interaction
between these pathways in agonist-stimulated tone.
PMID: 14982964 [PubMed - as supplied by publisher]