Comparison of H2O2-induced vasoconstriction in the abdominal aorta and mesenteric artery of the mouse

Abstract

Hydrogen peroxide (H(2)O(2)) is generally perceived as an arterial vasodilator. Due to the emerging importance of H(2)O(2) as a possible vasoconstrictor, we examined whether H(2)O(2) constricts both the abdominal aorta and superior mesenteric artery and postulated that H(2)O(2) is a ubiquitous constrictor of quiescent mouse arteries. Moreover, we postulated that KCl depolarization discloses and/or exaggerates H(2)O(2)-induced constriction. Under quiescent conditions, H(2)O(2) constricted the mouse abdominal aorta but not the mesenteric artery. Vessel depolarization (a) exaggerated this constrictor response in the aorta, and (b) unmasked a contractile response in the mesenteric artery. Our final hypothesis tested whether tyrosine kinases, mitogen-activated protein kinases (MAPKs), and/or Rho-kinase are uniformly involved in H(2)O(2)-induced vasoconstriction. We observed a marked difference in the ability of tyrosine kinase inhibitor to block H(2)O(2)-induced vasoconstriction. p38 and ERK 1/2MAPK inhibitors reduced the maximal response to H(2)O(2), whereas JNK inhibitor had no effect. Finally, Rho-kinase inhibitor decreased the H(2)O(2) response in the mesenteric artery but not in the aorta. These data demonstrate a variable yet tightly regulated H(2)O(2) vasoconstrictor effect. Furthermore, we found that p38, ERK 1/2 and Rho-kinase play a role in H(2)O(2) constriction, which may be critical pathways involved in H(2)O(2)-induced constriction across vascular beds.