Comparison of H2O2-induced vasoconstriction in the abdominal aorta and mesenteric artery of the mouse.
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.
Ardanaz
Noelia
N
Hypertension and Vascular Research Division, Henry Ford Health System, Detroit, MI 48202-2689, USA.
Beierwaltes
William H
WH
Pagano
Patrick J
PJ
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011189:Potassium Chloride / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D054460:rho-Associated Kinases