Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.

Autor: Bachman NP; Department of Kinesiology, Colorado Mesa University, Grand Junction, CO, USA.; Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA., Ketelhut NB; Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA., Blomquist M; Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.; Biomedical Sciences Department, Rocky Vista University, 255 E. Center St., Ivins, UT, 84738, USA., Terwoord JD; Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA. jterwoord@rvu.edu.; Biomedical Sciences Department, Rocky Vista University, 255 E. Center St., Ivins, UT, 84738, USA. jterwoord@rvu.edu.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Dec; Vol. 46 (6), pp. 6317-6329. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1007/s11357-024-01240-x
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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