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.
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http://dx.doi.org/10.1007/s11357-024-01240-x | DOI Listing |
BJOG
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Women's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.
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Mol Cell Biochem
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Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000, Kragujevac, Serbia.
As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10 mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os.
View Article and Find Full Text PDFJ Cardiothorac Vasc Anesth
December 2024
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. Electronic address:
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Design: A systematic review.
Setting: A search of PubMed, Embase, and the Cochrane Library from inception to May 3, 2024.
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January 2025
Unidad de Investigación en Atención Primaria de Salamanca (APISAL), Gerencia de Atención Primaria de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, España; Red de Investigación en Cronicidad, Atención Primaria y Promoción de la Salud (RICAPPS) Salamanca, España; Departamento de Medicina, Universidad de Salamanca, Salamanca, España.
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Anal Chim Acta
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Department of Pharmaceutical Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland.
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