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Assessment of Human Adipose Tissue Microvascular Function Using Videomicroscopy
Published on: September 29, 2017
Hypertension preserves the magnitude of microvascular flow-mediated dilation following transient elevation in
William E Hughes1,2, Natalya Zinkevich2,3, David D Gutterman1,2,4
1Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Insights
Transient increases in intraluminal pressure impair flow-mediated dilation (FMD) in coronary artery disease (CAD) and non-CAD arterioles. However, hypertension preserves FMD by shifting the dilation mechanism from nitric oxide (NO) to hydrogen peroxide (H2O2).
Area of Science:
- Vascular Physiology
- Cardiovascular Research
- Hypertension Studies
Background:
- Flow-mediated dilation (FMD) assesses endothelial function, crucial for cardiovascular health.
- Coronary artery disease (CAD) and hypertension are major risk factors for endothelial dysfunction.
- Understanding how pressure changes affect FMD in different patient groups is vital for cardiovascular disease management.
Purpose of the Study:
- To investigate the impact of transient increases in intraluminal pressure (IILP) on FMD in resistance arterioles.
- To compare the response of arterioles from non-CAD, CAD, and hypertensive non-CAD individuals.
- To elucidate the underlying mechanisms of FMD changes under simulated hypertensive conditions.
Main Methods:
- Resistance arterioles were isolated from human adipose and atrial tissues.
- IILP was simulated by applying 150 mmHg for 30 minutes.
- FMD and endothelial-independent dilation were measured before and after IILP exposure, with pharmacological interventions (L-NAME, peg-cat) used to probe dilation pathways.
Main Results:
- IILP significantly reduced FMD in both non-CAD and CAD arterioles.
- Arterioles from hypertensive non-CAD subjects showed no reduction in maximal FMD after IILP.
- In hypertensive non-CAD arterioles, nitric oxide (NO) mediated FMD pre-IILP, while hydrogen peroxide (H2O2) mediated it post-IILP.
Conclusions:
- Acute exposure to increased intraluminal pressure attenuates FMD in resistance arterioles from non-CAD and CAD individuals.
- Hypertension in non-CAD individuals preserves FMD magnitude following IILP due to a compensatory shift from NO to H2O2 signaling.
- These findings highlight a protective mechanism in hypertensive individuals that warrants further investigation in cardiovascular health.
Objective:
The objective of this study was to measure flow-mediated dilation (FMD) prior to and following transient increases in intraluminal pressure (IILP) in resistance arterioles isolated from subjects with and without coronary artery disease (CAD) (CAD and non-CAD) and non-CAD subjects with hypertension.
Methods:
Arterioles were isolated from discarded surgical tissues (adipose and atrial) from patients without coronary artery disease (non-CAD; ≤1 risk factor, excluding hypertension), with CAD, and non-CAD patients with hypertension (hypertension as the only risk factor). To simulate transient hypertension, increased IILP was generated (150 mmHg, 30 min) by gravity. Arterioles were constricted with endothelin-1, followed by FMD and endothelial-independent dilation prior to and following exposure to IILP.
Results:
IILP reduced FMD in non-CAD and CAD arterioles relative to pre-IILP (p <.05 at 100 cmH2 O). In contrast, arterioles from non-CAD hypertensive subjects exhibited no reduction in maximal FMD following IILP (p = .84 at 100 cmH2 O). FMD was reduced by L-NAME prior to IILP in non-CAD hypertensive patients (p < .05 at 100 cmH2 O); however, following IILP, FMD was inhibited by peg-cat (p < .05 at 100 cmH2 O), indicating a switch from NO to H2 O2 as the mechanism of dilation.
Conclusions:
Acute exposure (30 min) to IILP (150 mmHg) attenuates the magnitude of FMD in non-CAD and CAD resistance arterioles. The presence of clinically diagnosed hypertension in non-CAD resistance arterioles preserves the magnitude of FMD following IILP as a result of a compensatory switch from NO to H2 O2 as the mechanism of dilation.
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