Abstract 12848: Role of ROCK in Sustained Vasoconstriction of Resistance Artery in Patients with Essential Hypertension
Background: Sustainedvasoconstriction of pulmonary artery has been shown to be substantially related to the onset and progression of pathological condition in patients with pulmonary hypertension. Meanwhile, there is no clinical evidence concerning the relationship of sustained arterial vasoconstriction with essential hypertension, although it is well known that increased peripheral arterial resistance plays critical role to increase blood pressure. Recent studies suggest that Rho-associated kinase (ROCK) is involved in the pathogenesis in pulmonary hypertension. The purpose of this study is to determine whether arterial vasoconstriction is sustained in patients with essential hypertension and ROCK is involved in the mechanism in humans.
Methods and results: We evaluated the sustained vasoconstriction by measuring forearm blood flow (FBF) response to phenylephrine, a selective α1-adrenergic agonist, with or without co-infusion of fasudil, a specific ROCK inhibitor, in normotensive (n=16, 40.8±1.5 yrs) and hypertensive subjects (n=10, 42.0±4.4 yrs). FBF was measured using a strain-gauge plethysmograph. Intra-arterial infusion of phenylephrine substantially decreased FBF at 5 min after infusion compared to each baseline in both normotensive and hypertensive subjects (5.7±0.7 to 3.5±0.4 mL/min per 100 mL tissue; 5.3±0.6 vs. 2.4±0.4 mL/min per 100 mL tissue; p≤0.0001 respectively). In normotensive subjects, phenylephrine-evoked arterial vasoconstriction was sustained during 15 min of continuous infusion, but the vasoconstriction was disappeared at 20 min. In hypertensive subjects, on the other hand, the phenylephrine-evoked vasoconstriction was fully sustained during the continuous infusion of phenylephrine. Co-infusion of fasudil diminished the difference of FBF responses to phenylephrine between the two groups.
Conclusions: These findings suggest that vasoconstriction in resistance artery is sustained in patients with essential hypertension and ROCK is substantially involved in the mechanism, indicating that inhibition of ROCK could protect from cardiovascular damage induced by ROCK-mediated sustained arterial vasoconstriction in patients with essential hypertension.
- © 2013 by American Heart Association, Inc.