| First Author | Gödecke A | Year | 1998 |
| Journal | Circ Res | Volume | 82 |
| Issue | 2 | Pages | 186-94 |
| PubMed ID | 9468189 | Mgi Jnum | J:46061 |
| Mgi Id | MGI:1197044 | Doi | 10.1161/01.res.82.2.186 |
| Citation | Godecke A, et al. (1998) Coronary hemodynamics in endothelial NO synthase knockout mice. Circ Res 82(2):186-94 |
| abstractText | For the specific analysis of endothelial NO synthase (eNOS) function in the coronary vasculature, we generated a mouse homozygous for a defective eNOS gene (eNOS-/-). Western blot as well as immunohistochemical staining revealed the absence of eNOS protein in eNOS-/-mice. Aortic endothelial cells derived from eNOS-/-mice displayed only background levels of NOx formation compared with wild-type (WT) cells (88 versus 1990 pmol NOx h(- 1)/mg protein(-1)), eNOS-/-mice were hypertensive (mean arterial pressure, 135+/-15 versus 107+/-8 mm Hg in WT) without the development of cardiac hypertrophy. Coronary hemodynamics, analyzed in Langendorff-perfused hearts, showed no differences either in basal coronary flow or in maximal and repayment flow of reactive hyperemia. Acute NOS inhibition with N-omega-nitro-L-arginine methyl ester (L-NAME) in WT hearts substantially reduced basal flow and reactive hyperemia. The coronary response to acetylcholine (ACh) (500 nmol/L) was biphasic: An initial vasoconstriction (now, -35%) in WT hearts was followed by sustained vasodilation (+190%). L-NAME significantly reduced vasodilation in WT hearts (+125%) but did not alter the initial vasoconstriction. In eNOS-/-hearts, the initial vasoconstriction was augmented (-70%), whereas the ACh-induced vasodilation was nor affected, Inhibition of cyclooxygenase with diclofenac converted the ACh-induced vasodilation into vasoconstriction (-49% decrease of basal no iii). This effect was even more pronounced in eNOS-/- hearts (-71%). Our results demonstrate that (1) acute inhibition of eNOS reveals a role for NO in setting the basal coronary vascular tone as well as participation in reactive hyperemia and the response to ACh; (2) chronic inhibition of NO formation in eNOS-/-mutant mice induces no changes in basal coronary now and reactive hyperemia, suggesting the activation of important compensatory mechanisms; and (3) prostaglandins are the main mediators Of the ACh-induced vasodilation in both WT and eNOS-/- mice. |
