Endothelial and myogenic regulation of coronary artery tone in the mouse.
Ventricular septal (150-200 microm) arteries were isolated from the hearts of six-week-old CD-1 mice and mounted on a pressure myograph. Equilibration of the vessels at 70 mm Hg for 60 min resulted in the development of spontaneous myogenic tone. Maximum tone observed in these vessels greatly exceeded that previously reported in septal arteries from rats. Inhibition of endothelin ET(A) and endothelin ET(B) receptors with bosentan (1 and 10 microM) reduced basal tone. Endothelin release required intact endothelial cells. The alpha(1)-adrenceptor selective agonists phenylephrine and methoxamine did not cause change in coronary tone, while the alpha(2)-adrenceptor selective agonists 6-allyl-2-amino5,6,7, 8-tetrahydro-4H-thiazolo-[4,5-d]azepin-dihydrochloride (BHT 920) and clonidine produced vasodilatation. Noradrenaline (1 nM-10 microM) induced a concentration-dependent vasodilatation, which was inhibited by concurrent treatment with yohimbine (10 microM) and propranolol (20 microM). Vasodilatation due to BHT 920 was abolished with vessel denudation, indicating the endothelial location of alpha(2)-adrenoceptors. Acetylcholine (1 nM-10 microM) caused an endothelium dependent vasodilatation; inhibition of nitric oxide synthase with N(omega)-nitro-L-arginine methyl ester attenuated this response. The endothelium-dependent vasodilators bradykinin and substance P produced no vasomotor effect in mouse coronary arteries. Differences between human and murine responses may impact on the relevance of the mouse coronary artery for use as a potential model of human coronary vessel diseases.
Lui
A H
AH
Department of Pharmacology and Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada. amyh@unixg.ubc.ca
McManus
B M
BM
Laher
I
I
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011950:Receptors, Cholinergic / Q000187:drug effects; D017466:Receptors, Endothelin / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011950:Receptors, Cholinergic; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; D009569:Nitric Oxide