Vascular reactivity of isolated thoracic aorta of the C57BL/6J mouse

We characterized the thoracic aorta from the C57BL/6J mouse, a strain used commonly in the generation of genetically altered mice, in response to vaso active substances. Strips of aorta were mounted in tissue baths for measure ment of isometric contractile force. Cumulative concentration-response curv es to agonists were generated to observe contraction, or relaxation in tiss ues contracted with phenylephrine or prostaglandin F-2 alpha (PGF(2 alpha)) . In endothelium-denuded strips, the order of agonist contractile potency ( -log EC50 [M]) was norepinephrine > phenylephrine = 5-hydroxytryptamine. do pamine. PGF(2 alpha) > isoproterenol > KCl. Angiotensin II and endothelin-1 were weakly efficacious (15% of maximum phenylephrine contraction), as wer e UK14,304, clonidine, histamine, and adenosine. In endothelium-intact stri ps, agonists still caused contraction and both angiotensin II and endotheli n-1 remained ineffective. In experiments focusing on angiotensin II, angiot ensin II-induced contraction was abolished by the AT(1) receptor antagonist losartan (1 mu M) but was not enhanced in the presence of the AT(2) recept or antagonist PD123319 (0.1 mu M), tyrosine phosphatase inhibitor orthovana date (1 mu M) or when angiotensin II was given noncumulatively. Prazosin ab olished isoproterenol-induced contraction and did not unmask isoproterenol- induced relaxation. Angiotensin II and endothelin-1 did not cause endotheli um-dependent or -independent relaxation in phenylephrine- or PGF(2 alpha)-c ontracted tissues. Acetylcholine but not histamine, dopamine, or adenosine caused an endothelium-dependent vascular relaxation. These experiments prov ide information as to the vascular reactivity of the normal mouse thoracic aorta and demonstrate that the mouse aorta differs substantially from rat a orta in response to isoproterenol, angiotensin II, endothelin-1, histamine, and adenosine.