Journal article
Hydrogen sulfide-dependent microvascular vasodilation is improved following chronic sulfhydryl-donating antihypertensive pharmacotherapy in adults with hypertension
American journal of physiology. Heart and circulatory physiology, Vol.321(4), pp.H728-H734
10/01/2021
DOI: 10.1152/ajpheart.00404.2021
PMCID: PMC8803310
PMID: 34477463
Abstract
Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (H
S)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE inhibitor (SH-ACE inhibitor) improves endothelial function in preclinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment on H
S-dependent vasodilation in humans with hypertension. We hypothesized that SH-ACE-inhibitor treatment would improve H
S-mediated endothelium-dependent vasodilation. Ten adults with hypertension [1 woman and 9 men; 56 ± 9 yr; systolic blood pressure (SBP): 141 ± 8.5 mmHg; diastolic blood pressure (DBP): 90.3 ± 6 mmHg] were treated (16 wk) with the SH-ACE-inhibitor captopril. Red blood cell flux (laser-Doppler flowmetry) was measured continuously during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (ACh; 10
to 10
M) alone (control) and in combination with an inhibitor of enzymatic H
S production [10
M aminooxyacetate (AOAA)] preintervention and postintervention. Cutaneous vascular conductance (CVC; flux/mmHg) was calculated and normalized to the site-specific maximal CVC (0.028 M sodium nitroprusside and local heat to 43°C). Area under the curve was calculated using the trapezoid method. The 16-wk SH-ACE-inhibitor treatment resulted in a reduction of blood pressure (systolic BP: 129 ± 10 mmHg; diastolic BP: 81 ± 9 mmHg, both
< 0.05). Preintervention, inhibition of H
S production had no effect on ACh-induced vasodilation (316 ± 40 control vs. 322 ± 35 AU AOAA;
= 0.82). Captopril treatment improved ACh-induced vasodilation (316 ± 40 pre vs. 399 ± 55 AU post;
= 0.04) and increased the H
S-dependent component of ACh-induced vasodilation (pre: -6.6 ± 65.1 vs. post: 90.2 ± 148.3 AU,
= 0.04). These data suggest that SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in adults with hypertension, in part via H
S-dependent mechanisms.
This is the first study to prospectively assess the effects of sulfhydryl antihypertensive treatment on microvascular endothelial function in adults with hypertension. Our data suggest that 16 wk of SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in middle-aged adults with hypertension, in part via H
S-dependent mechanisms.
Details
- Title: Subtitle
- Hydrogen sulfide-dependent microvascular vasodilation is improved following chronic sulfhydryl-donating antihypertensive pharmacotherapy in adults with hypertension
- Creators
- Gabrielle A Dillon - Pennsylvania State UniversityAnna E Stanhewicz - Pennsylvania State UniversityCorinna Serviente - Pennsylvania State UniversityJody L Greaney - Pennsylvania State UniversityLacy M Alexander - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.321(4), pp.H728-H734
- DOI
- 10.1152/ajpheart.00404.2021
- PMID
- 34477463
- PMCID
- PMC8803310
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- R21 MH123928 / NIMH NIH HHS R00 HL133414 / NHLBI NIH HHS NIH HL093238 / HHS | National Institutes of Health (NIH) NIH T-32-5T32AG049676 / HHS | National Institutes of Health (NIH) R01 HL093238 / NHLBI NIH HHS T32 AG049676 / NIA NIH HHS
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259395202771
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