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Exercise vasodilation is greater in women: contributions of nitric oxide synthase and cyclooxygenase

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Abstract

Purpose

We hypothesized exercise vasodilation would be greater in women due to nitric oxide synthase (NOS) and cyclooxygenase (COX) signaling.

Methods

45 healthy adults (23 women, W, 22 men, M, 26 ± 1 years) completed two 10-min trials of dynamic forearm exercise at 15 % intensity. Forearm blood flow (FBF; Doppler ultrasound), arterial pressure (brachial catheter), and forearm lean mass were measured to calculate relative forearm vascular conductance (FVCrel) = FBF 100 mmHg−1 100 g−1 lean mass. Local intra-arterial infusion of L-NMMA or ketorolac acutely inhibited NOS and COX, respectively. In Trial 1, the first 5 min served as control exercise (CON), followed by 5 min of L-NMMA or ketorolac over the last 5 min of exercise. In Trial 2, the remaining drug was infused during 5–10 min, to achieve combined NOS–COX inhibition (double blockade, DB).

Results

Are mean ± SE. Women exhibited 29 % greater vasodilation in CON (ΔFVCrel, 19 ± 1 vs. 15 ± 1, p = 0.01). L-NMMA reduced ΔFVCrel (p < 0.001) (W: Δ −2.3 ± 1.3 vs. M: Δ −3.7 ± 0.8, p = 0.25); whereas, ketorolac modestly increased ΔFVCrel (p = 0.04) similarly between sexes (W: Δ 1.6 ± 1.1 vs. M: Δ 2.0 ± 1.6, p = 0.78). DB was also found to be similar between the sexes (p = 0.85).

Conclusion

These data clearly indicate women produce a greater exercise vasodilator response. Furthermore, contrary to experiments in animal models, these data are the first to demonstrate vascular control by NOS and COX is similar between sexes.

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Abbreviations

ASAs:

Acetylsalicylic acid

BMI:

Body mass index

CON:

Control exercise

COX:

Cyclooxygenase

DEXA:

Dual-energy X-ray absorptiometry

DB:

Double blockade, NOS–COX inhibition condition

ECG:

Electrocardiogram

EDHF:

Endothelium-derived hyperpolarizing factor

FBF:

Forearm blood flow

FVC:

Forearm vascular conductance

KETO:

Ketorolac, COX inhibition condition

L-NMMA:

L-NG-monomethyl arginine, NOS inhibition condition

MAP:

Mean arterial pressure

MBV:

Mean blood velocity

MVC:

Maximal voluntary contraction

NOS:

Nitric oxide synthase

NSAIDs:

Non-steroidal anti-inflammatory drugs acetylsalicylic acid

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Acknowledgments

We would like to thank the subjects for their time and effort. We would also like to acknowledge Meghan Crain, Garrett Peltonen, Joshua Trierweiler, and Cameron Rousseau, for their help in data collection. The Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), supported the described project grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding: NIH HL-105820.

Conflict of interest

The authors have no conflicts of interests and nothing to disclose.

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Correspondence to J. Mikhail Kellawan.

Additional information

Communicated by Massimo Pagani.

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Kellawan, J.M., Johansson, R.E., Harrell, J.W. et al. Exercise vasodilation is greater in women: contributions of nitric oxide synthase and cyclooxygenase. Eur J Appl Physiol 115, 1735–1746 (2015). https://doi.org/10.1007/s00421-015-3160-6

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  • DOI: https://doi.org/10.1007/s00421-015-3160-6

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