Endothelium-dependent contractions occur in the aorta of wild-type and COX2-/- knockout but not COX1-/- knockout mice.
The present experiments were designed to determine whether or not endothelium-dependent contractions can be evoked in the aorta of the mouse, and if so, whether or not deleting the COX1 gene affects the response. Sex differences in the response were also examined. Rings of murine aorta were suspended in a Halpern-Mulvany myograph for recording of isometric force. In the aorta of the male wild type C57BL/b6 mice (36-40 weeks old), both acetylcholine and the calcium ionophore caused endothelium-dependent increases in force in the presence of L-NAME, and these were inhibited by valeryl salicylate (a selective COX1 inhibitor) and S18886 (a selective antagonist of TP receptors). Such endothelium-dependent contraction was absent in the aorta of COX1 knockout mice and present in that of COX2 knockout mice. Similar results were obtained in aortas of female wild-type, COX2 and COX1 knockout mice. These experiments reveal the existence of EDCF-mediated contractions in arteries of the mouse. These contractions, as in the aorta of the spontaneously hypertensive rat, are caused by endogenous agonists(s) of TP receptors produced by cyclooxygenase 1, because they are observed in the aortas of COX2 knockout mice but not in aortas of COX1 knockout mice. The present study provides direct evidence that COX1 is indeed the isoform of cyclooxygenase responsible for the production of EDCF.
Tang
Eva H C
EH
Department of Pharmacology, University of Hong Kong, Hong Kong.
Ku
David D
DD
Tipoe
George L
GL
Feletou
Michel
M
Man
Ricky Y K
RY
Vanhoutte
Paul M
PM
D000818:Animals; D001011:Aorta / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D012727:Sex Characteristics; D014661:Vasoconstriction
D016232:Endothelins; D000001:Calcimycin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019331:NG-Nitroarginine Methyl Ester