Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice

Previous studies have demonstrated that responses to endothelium-dependent vasodilators are absent in the aortas from mice deficient in expression of endothelial nitric oxide synthase (eNOS -/- mice), whereas responses in the cerebral microcirculation are preserved. We tested the hypothesis that in the absence of eNOS, other vasodilator pathways compensate to preserve endo thelium-dependent relaxation in the coronary circulation. Diameters of isol ated, pressurized coronary arteries from eNOS -/-, eNOS heterozygous (+/-), and wild-type mice (eNOS +/+ and C57BL/6J) were measured by video microsco py. ACh (an endothelium-dependent agonist) produced vasodilation in wild-ty pe mice. This response was normal in eNOS +/- mice and was largely preserve d in eNOS -/- mice. Responses to nitroprusside were also similar in arterie s from eNOS +/+, eNOS +/-, and eNOS -/- mice. Dilation to ACh was inhibited by N-G-nitro-L-arginine, an inhibitor of NOS in control and eNOS -/- mice. In contrast, trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on responses in wild-type mice. Indomethacin, an inhibit or of cyclooxygenase, decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus, in the absence of eNOS, dilation of coronary art eries to ACh is preserved by other vasodilator mechanisms.