Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18–30 years, 6F/6M) and older (60–80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase. Fasudil lowered SBP in older adults compared to placebo (saline) (2-h post-infusion: 125 ± 4 vs. 133 ± 4 mmHg, P < 0.05), whereas fasudil had no impact on SBP in young adults. Immediately following fasudil infusion, there was a transient reduction in mean arterial pressure (MAP) in young adults that was no longer evident 1-h post-infusion. In older adults, MAP remained lower throughout the fasudil visit compared to placebo (2-h post-infusion: 93 ± 3 vs. 100 ± 3 mmHg, P < 0.05) such that age-related differences in SBP and MAP were abolished. Aortic stiffness (carotid-femoral pulse wave velocity) was not altered by fasudil when central MAP was included as a covariate in analyses. Fasudil reduced forearm vascular resistance in older (2-h post-infusion: 3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min, P < 0.05) but not young (4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min) adults, which was accompanied by an increase in brachial artery diameter only in older adults. Brachial artery flow-mediated dilation was not affected by fasudil in either group. These findings indicate that Rho-kinase inhibition reduces SBP in healthy older but not young adults, which is associated with a concomitant reduction in forearm vascular resistance.

在临床前研究中，Rho 激酶与高血压的发展有关，并可能导致与年龄相关的血压升高。本研究检验了 Rho 激酶导致健康老年人收缩压 （SBP） 升高的假设。年轻 （18-30 岁，6F/6M） 和老年人 （60-80 岁，7F/6M） 参加了一项双盲、安慰剂对照的交叉研究，使用静脉输注法舒地尔来抑制 Rho 激酶。与安慰剂（生理盐水）相比，法舒地尔降低了老年人的 SBP（输注后 2 小时：125 ± 4 vs. 133 ± 4 mmHg，P < 0.05）， 而法舒地尔对年轻人的 SBP 没有影响。输注法舒地尔后，年轻人的平均动脉压 （MAP） 立即短暂降低，输注后 1 小时不再明显。在老年人中，与安慰剂相比，整个法舒地尔就诊期间 MAP 保持较低 （输注后 2 小时：93 ± 3 vs. 100 ± 3 mmHg，P < 0.05）， 因此消除了 SBP 和 MAP 的年龄相关差异。当中央 MAP 作为协变量包含在分析中时，法舒地尔不会改变主动脉僵硬（颈股脉搏波速度）。法舒地尔降低了老年人的前臂血管阻力 （输注后 2 小时：3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min，P < 0.05）但不年轻 （4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min） 成人，仅伴随着老年人肱动脉直径的增加。两组肱动脉血流介导的扩张均不受法舒地尔的影响。这些发现表明，Rho 激酶抑制可降低健康老年人的 SBP，但不降低年轻人的 SBP，这与前臂血管阻力的降低有关。