Abstract
Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective: To assess effects of antihypertensive pharmacotherapy on eNOS- and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods: Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mm Hg), 12 unmedicated hypertensive (SBP 142±2 mm Hg), and 12 medicated hypertensive (SBP 120±2 mm Hg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux, measured during local heating (42°C) and ACh dose-response protocols, was normalized to CVC (flux MAP−1) and a percentage of maximal vasodilation (%CVCmax). Results: Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition, there was no difference in ACh-mediated vasodilation between groups. Compared to the normotensives, local heat-induced vasodilation was attenuated in the hypertensives (P<.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished (P=.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive (P=.014) and medicated subjects (P=.004). Conclusions: In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO-dependent and NO-independent mechanisms, but did not improve maximal vasodilator capacity.
| Original language | English (US) |
|---|---|
| Article number | e12382 |
| Journal | Microcirculation |
| Volume | 24 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 2017 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Molecular Biology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
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Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO-dependent and NO-independent mechanisms. / Craighead, Daniel H.; Smith, Caroline J.; Alexander, Lacy M.
In: Microcirculation, Vol. 24, No. 7, e12382, 10.2017.Research output: Contribution to journal › Article
TY - JOUR
T1 - Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO-dependent and NO-independent mechanisms
AU - Craighead, Daniel H.
AU - Smith, Caroline J.
AU - Alexander, Lacy M.
PY - 2017/10
Y1 - 2017/10
N2 - Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective: To assess effects of antihypertensive pharmacotherapy on eNOS- and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods: Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mm Hg), 12 unmedicated hypertensive (SBP 142±2 mm Hg), and 12 medicated hypertensive (SBP 120±2 mm Hg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux, measured during local heating (42°C) and ACh dose-response protocols, was normalized to CVC (flux MAP−1) and a percentage of maximal vasodilation (%CVCmax). Results: Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition, there was no difference in ACh-mediated vasodilation between groups. Compared to the normotensives, local heat-induced vasodilation was attenuated in the hypertensives (P<.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished (P=.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive (P=.014) and medicated subjects (P=.004). Conclusions: In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO-dependent and NO-independent mechanisms, but did not improve maximal vasodilator capacity.
AB - Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective: To assess effects of antihypertensive pharmacotherapy on eNOS- and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods: Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mm Hg), 12 unmedicated hypertensive (SBP 142±2 mm Hg), and 12 medicated hypertensive (SBP 120±2 mm Hg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux, measured during local heating (42°C) and ACh dose-response protocols, was normalized to CVC (flux MAP−1) and a percentage of maximal vasodilation (%CVCmax). Results: Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition, there was no difference in ACh-mediated vasodilation between groups. Compared to the normotensives, local heat-induced vasodilation was attenuated in the hypertensives (P<.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished (P=.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive (P=.014) and medicated subjects (P=.004). Conclusions: In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO-dependent and NO-independent mechanisms, but did not improve maximal vasodilator capacity.
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U2 - 10.1111/micc.12382
DO - 10.1111/micc.12382
M3 - Article
C2 - 28510986
AN - SCOPUS:85030761779
VL - 24
JO - Microcirculation
JF - Microcirculation
SN - 1073-9688
IS - 7
M1 - e12382
ER -