Key result
Endothelial nitric oxide synthase blockade with L-NMMA reduced brachial artery vasodilation during handgrip exercise by up to 60% at higher intensities (from 10.7% to 4.4% at 24kg).
Why the study?
Does eNOS blockade reduce brachial artery vasodilation during incremental handgrip exercise in healthy volunteers?
Does eNOS blockade reduce brachial artery vasodilation during incremental handgrip exercise in healthy volunteers?
Absolute Event Rate: 4.4% vs 10.7%
Handgrip exercise provides a multi-level approach to elevate shear stress and determine endothelium-dependent vasodilatory capacity, which is significantly mediated by NO at higher work rates.
NO mediates high-intensity handgrip vasodilation in healthy subjects; leaves open protocol utility for clinical endothelial assessment.
PURPOSE: In the peripheral circulation, nitric oxide (NO) is released in response the shear stress across vascular endothelial cells. While non-invasive assessment of NO bioavailability is conventionally performed using the post-occlusion flow-mediated vasodilation (FMD) test, this paradigm is limited in that it provides only a singular stimulus-response value (i.e. cumulative shear that yields a single % vasodilation). We sought to develop a handgrip exercise paradigm that provokes incremental levels of shear within a single protocol to assess more comprehensively the vascular stimulus-response relationship, and to document the role of NO in this paradigm. METHODS: In six young (24 ± 1 yrs) healthy volunteers, we examined brachial artery (BA) vasodilation in response to handgrip exercise with and without endothelial nitric oxide synthase (eNOS) blockade (intra-arterial infusion of L-NMMA at 0.5 mg/dl forearm volume/min). Ultrasound Doppler was used to evaluate BA diameter and blood velocity during dynamic handgrip exercise (4-8-12-16-20-24 kg, 1 Hz, 3-min stages), intensities which represented 8-50% of maximal voluntary contraction. RESULTS: BA vasodilation was unaffected by NO blockade at lower exercise intensities (4-8-12 kg), but was blunted by 30-60% during NO blockade at higher intensities (3.7 ± 1.4 to 2.6 ± 1.4%, 16kg; 8.0 ± 2.2 to 2.9 ± 1.7%, 20kg; 10.7 ± 2.2 to 4.4 ± 1.3%, 24kg). This reduction in vasodilatory capacity was evident even when normalized for the L-NMMA-mediated decrement in shear rate. CONCLUSIONS: In the presence of eNOS inhibition, BA vasodilation during handgrip exercise was reduced by up to 60% at the higher work rates, suggesting a significant, but not exclusive, role of NO in this handgrip exercise model. These findings lend credence to the use of this exercise paradigm as a multi-level approach by which incrementally elevate shear stress and subsequently determine endothelium-dependant vasodilatory capacity in humans. Funded in part by NIH PO1 HL-091830, AHA 0835209N, and TRDRP 15RT-0100.
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Wray et al. (2010) studied Healthy (n=6). eNOS blockade (intra-arterial L-NMMA) vs. Without eNOS blockade was evaluated on Brachial artery vasodilation at 24kg handgrip exercise intensity. Endothelial nitric oxide synthase blockade with L-NMMA reduced brachial artery vasodilation during handgrip exercise by up to 60% at higher intensities (from 10.7% to 4.4% at 24kg).
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