Ultrasound stimulates formation and release of vasoactive compounds in brain endothelial cells.

Abstract

Stroke outcome is improved by therapeutic ultrasound. This benefit is presumed to be principally from ultrasound-mediated thrombolysis. We hypothesized that the therapeutic benefit of ultrasound in stroke may, in part, be mediated by the release of beneficial vasoactive substances. Accordingly, we investigated the effect of ultrasound on levels of cytochrome P-450, lipoxygenase, and cyclooxygenase metabolites of arachidonic acid as well as adenosine release and endothelial nitric oxide synthase (eNOS) phosphorylation in primary brain endothelial cells in vitro. Brain endothelial cells were exposed to 1.05-MHz ultrasound at peak rarefactional acoustic pressure amplitudes of 0.35, 0.55, 0.90, and 1.30 MPa. Epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraenoic acids (HETEs), PGE2, adenosine, nitrate/nitrite, and eNOS phosphorylation were measured after ultrasound exposure. Levels of 8,9-EET, 11,12-EET, and 14,15-EET increased by 230 ± 28%, 240 ± 30%, and 246 ± 31% (P < 0.05), respectively, whereas 5-HETE and 15-HETE levels were reduced to 24 ± 14% and 10 ± 3% (P < 0.05), respectively, compared with cells not exposed to ultrasound. PGE2 levels were reduced to 56 ± 14% of control. Adenosine increased more than sixfold after ultrasound exposure compared with unstimulated cells (1.36 ± 0.22 vs. 0.37 ± 0.10 ng/ml, P < 0.05), nitrate/nitrite was below levels of quantification, and eNOS phosphorylation was not altered significantly. Our results suggest that ultrasound may enhance tissue perfusion during stroke by augmenting the generation of vasodilator compounds and inhibiting that of vasoconstrictors. Such regulation supports a beneficial role for therapeutic ultrasound in stroke independent of its effect on the occlusive thrombus.

• Authors: Catherine M Davis, Azzdine Y Ammi, Nabil J Alkayed, Sanjiv Kaul
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 309 Issue 4 Pg. H583-91 (Aug 15 2015) ISSN: 1522-1539 [Electronic] United States
• PMID: 26092990 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Hydroxyeicosatetraenoic Acids
• Cytochrome P-450 Enzyme System
• Lipoxygenase
• Nitric Oxide Synthase Type III
• Prostaglandin-Endoperoxide Synthases
• Adenosine
• Dinoprostone

Topics

• Adenosine (metabolism)
• Animals
• Brain (blood supply, cytology, radiation effects)
• Cells, Cultured
• Cytochrome P-450 Enzyme System (metabolism)
• Dinoprostone (metabolism)
• Endothelial Cells (metabolism, radiation effects)
• Endothelium, Vascular (metabolism, radiation effects)
• Hydroxyeicosatetraenoic Acids (metabolism)
• Lipoxygenase (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Synthase Type III (metabolism)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Sound
• Vasodilation