Hydrogen sulfide-dependent microvascular vasodilation is improved following chronic sulfhydryl-donating antihypertensive pharmacotherapy in hypertensive adults.

Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (H2S)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE-inhibitor (SH-ACE-inhibitor) improves endothelial function in pre-clinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment on H2S-dependent vasodilation in hypertensive humans. We hypothesized that SH-ACE-inhibitor treatment would improve H2S-mediated endothelium-dependent vasodilation. Ten hypertensive adults (1W; 56±9yrs, Systolic BP: 141±8.5 mmHg; Diastolic BP: 90.3±6 mmHg) were treated (16 weeks) 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; 10-10-10-1 M) alone (control) and in combination with an inhibitor of enzymatic H2S production (10-3 M aminooxyacetate; AOAA) pre- and post-intervention. Cutaneous vascular conductance (CVC; flux/mmHg) was calculated and normalized to the site-specific maximal CVC (0.028M sodium nitroprusside and local heat to 43°C). Area-under-the-curve was calculated using the trapezoid method. The 16-week SH-ACE-inhibitor treatment resulted in a reduction of blood pressure (Systolic BP: 129±10 mmHg; Diastolic BP: 81 ±9 mmHg, both p<0.05). Pre-intervention, inhibition of H2S production had no effect on ACh-induced vasodilation (316±40 control vs 322±35 AU AOAA; p=0.82). Captopril treatment improved ACh-induced vasodilation (316±40 pre vs 399±55 AU post; p=0.04) and increased the H2S-dependent component of ACh-induced vasodilation (pre: -6.6 ± 65.1 vs post: 90.2 ± 148.3 AU, p=0.04). These data suggest that SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in hypertensive adults, in part via H2S-dependent mechanisms.

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ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-2006-925754 ◽

2006 ◽

Vol 54 (S 1) ◽

Author(s):

A Boldt ◽

A Scholl ◽

J Garbade ◽

ME Resetar ◽

FW Mohr ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ace Inhibitor ◽

Chronic Atrial Fibrillation ◽

Structural Remodeling ◽

Inhibitor Treatment

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Does ACE polymorphism influence blood pressure and S-creatinine under ACE-inhibitor treatment?

American Journal of Hypertension ◽

10.1016/s0895-7061(01)01743-5 ◽

2001 ◽

Vol 14 (11) ◽

pp. A75

Author(s):

B Suwelack

Keyword(s):

Blood Pressure ◽

Ace Inhibitor ◽

Ace Polymorphism ◽

Inhibitor Treatment

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Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin

Journal of Applied Physiology ◽

10.1152/japplphysiol.01257.2011 ◽

2012 ◽

Vol 112 (5) ◽

pp. 791-797 ◽

Cited By ~ 55

Author(s):

Anna E. Stanhewicz ◽

Rebecca S. Bruning ◽

Caroline J. Smith ◽

W. Larry Kenney ◽

Lacy A. Holowatz

Keyword(s):

Nitric Oxide ◽

Human Skin ◽

Oxidant Stress ◽

Local Heat ◽

Whole Body ◽

Mean Body Temperature ◽

Doppler Flowmetry ◽

Cutaneous Vasodilation ◽

Aged Skin ◽

Reflex Cutaneous Vasodilation

Functional constitutive nitric oxide synthase (NOS) is required for full expression of reflex cutaneous vasodilation that is attenuated in aged skin. Both the essential cofactor tetrahydrobiopterin (BH4) and adequate substrate concentrations are necessary for the functional synthesis of nitric oxide (NO) through NOS, both of which are reduced in aged vasculature through increased oxidant stress and upregulated arginase, respectively. We hypothesized that acute local BH4 administration or arginase inhibition would similarly augment reflex vasodilation in aged skin during passive whole body heat stress. Four intradermal microdialysis fibers were placed in the forearm skin of 11 young (22 ± 1 yr) and 11 older (73 ± 2 yr) men and women for local infusion of 1) lactated Ringer, 2) 10 mM BH4, 3) 5 mM ( S)-(2-boronoethyl)-l-cysteine + 5 mM Nω-hydroxy-nor-l-arginine to inhibit arginase, and 4) 20 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced. After a 1.0°C rise in oral temperature (Tor), mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and expressed as a percentage of maximum (%CVCmax; 28 mM sodium nitroprusside and local heat, 43°C). Vasodilation was attenuated at the control site of the older subjects compared with young beginning at a 0.3°C rise in Tor. BH4 and arginase inhibition both increased vasodilation in older (BH4: 55 ± 5%; arginase-inhibited: 47 ± 5% vs. control: 37 ± 3%, both P < 0.01) but not young subjects compared with control (BH4: 51 ± 4%CVCmax; arginase-inhibited: 55 ± 4%CVCmax vs. control: 56 ± 6%CVCmax, both P > 0.05) at a 1°C rise in Tor. With a 1°C rise in Tor, local BH4 increased NO-dependent vasodilation in the older (BH4: 31.8 ± 2.4%CVCmax vs. control: 11.7 ± 2.0%CVCmax, P < 0.001) but not the young (BH4: 23 ± 4%CVCmax vs. control: 21 ± 4%CVCmax, P = 0.718) subject group. Together these data suggest that reduced BH4 contributes to attenuated vasodilation in aged human skin and that BH4 NOS coupling mechanisms may be a potential therapeutic target for increasing skin blood flow during hyperthermia in older humans.

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