Distinct hydrogen peroxide-induced constriction in multiple mouse arteries: potential influence of vascular polarization

Abstract

It is a matter of controversy whether the reactive oxygen species hydrogen peroxide (H(2)O(2)) contributes to tone in the vasculature as a vasodilator or vasoconstricting factor. To address this, we hypothesized that H(2)O(2) can constrict quiescent, non-preconstricted blood vessels, but that the contractile response may be different across various vessel beds. As this variable response may be related to the quiescent state of polarization, we further tested whether partial KCl depolarization would unmask or potentiate H(2)O(2)-induced constriction. We harvested thoracic and abdominal aorta, the carotid and superior mesenteric artery from mice and placed them in myograph systems to measure contractile responses. Under quiescent conditions without pre-contraction, we found that H(2)O(2)-contracted abdominal aorta with a peak of 21 +/- 4.9% of the reference constriction to 100 mMKCl (p < 0.05), the thoracic aorta contracted by 9.1 +/- 3.6% (p < 0.05), the carotid artery contracted by 5.1 +/- 1.9% (p < 0.05), but there was no contraction in the mesenteric artery at any concentration of H(2)O(2) tested in the quiescent state. If the quiescent vessels were then partially depolarized using 30 or 100 mMKCl, we found a significant potentiation of the contractile response to H(2)O(2) of 3-7 fold in each of the abdominal, thoracic and carotid vessels, and an unmasking of a significant (71 +/- 6.9%, p < 0.05) contractile response to H(2)O(2) in the mesenteric artery. Thus, we found large variations in the ability of H(2)O(2) to constrict these quiescent arteries, but partial KCl depolarization either significantly exaggerated the H(2)O(2)-induced constriction, or in the otherwise refractory mesenteric, revealed an H(2)O(2)-provoked vasoconstriction. Thus, H(2)O(2) is a vasoconstrictor in quiescent or partially depolarized vessels. We conclude that H(2)O(2) elicits distinct constrictor effects across different vascular beds, and this may be due to their underlying state of polarization.