Nitric oxide synthase inhibition attenuates cutaneous vasodilation during postmenopausal hot flash episodes

Menopause. Sep-Oct 2010;17(5):978-82. doi: 10.1097/gme.0b013e3181d674d6.


Objective: The purpose of this study was to test the hypothesis that local inhibition of nitric oxide and prostaglandin synthesis attenuates cutaneous vasodilator responses during postmenopausal hot flash episodes.

Methods: Four microdialysis membranes were inserted into the forearm skin (dorsal surface) of eight postmenopausal women (mean +/- SD age, 51 +/- 7 y). Ringer solution (control), 10 mM ketorolac (Keto) to inhibit prostaglandin synthesis, 10 mM N-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase, and a combination of 10 mM Keto + 10 mM l-NAME were each infused at the separate sites. Skin blood flow at each site was indexed using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure and was expressed as a percentage of the maximal calculated CVC (CVCmax) obtained after infusion of 50 mM sodium nitroprusside at all sites at the end of the study. Data from 13 hot flash episodes were analyzed.

Results: At the control site, the mean +/- SD peak increase in CVC was 15.5% +/- 6% CVCmax units. This value was not different relative to the peak increase in CVC at the Keto site (13.0% +/- 5% CVCmax units; P = 0.09). However, the peak increase in CVC during hot flash episodes were attenuated at the l-NAME and l-NAME + Keto sites (7.4% +/- 4% and 8.7% +/- 7% CVCmax units, respectively) relative to both the control and the Keto sites (P < 0.05 for both comparisons). There were no significant differences in the peak increases in sweat rate between any of the sites (P = 0.24).

Conclusions: These data demonstrate that the mechanism for cutaneous vasodilation during hot flash episodes has a nitric oxide component. Increases in CVC despite the inhibition of prostaglandin synthesis suggest that prostaglandins do not contribute to cutaneous vasodilation during hot flash episodes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Hot Flashes / physiopathology*
  • Humans
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Postmenopause / physiology*
  • Prostaglandins / physiology
  • Vasodilation / physiology*


  • Prostaglandins
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester