Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO-dependent and NO-independent mechanisms

Daniel H. Craighead, Caroline J. Smith, Lacy M. Alexander

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Article numbere12382
JournalMicrocirculation
Volume24
Issue number7
DOIs
StatePublished - Oct 2017

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Vasodilation
Blood Pressure
Drug Therapy
Skin
Vasodilator Agents
Microvessels
Antihypertensive Agents
Microdialysis
Heating
Hot Temperature
Hypertension

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO-dependent and NO-independent mechanisms",
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.",
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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 journalArticle

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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