| First Author | Longo M | Year | 2005 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 288 |
| Issue | 5 | Pages | R1114-21 |
| PubMed ID | 15626780 | Mgi Jnum | J:97730 |
| Mgi Id | MGI:3576182 | Doi | 10.1152/ajpregu.00367.2004 |
| Citation | Longo M, et al. (2005) Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 288(5):R1114-21 |
| abstractText | Epidemiological studies have shown increased incidence of hypertension and coronary artery disease in growth-restricted fetuses during their adult life. A novel animal model was used to test the hypothesis regarding the role of an abnormal uterine environment in fetal programming of adult vascular dysfunction. Mice lacking a functional endothelial nitric oxide synthase (NOS3(-/-KO), where KO is knockout) and wild-type (WT) mice (NOS3(+/+WT)) were crossbred to produce homozygous NOS3(-/-KO), maternally derived heterozygous (NOS3(+/-mat), mother with NOS3 deficiency), paternally derived heterozygous (NOS3(+/-pat), normal mother), and NOS3(+/+WT) litters. Number of fetuses per litter was smaller in NOS3(-/-KO) and NOS3(+/-mat) compared with NOS3(+/-pat) and NOS3(+/+WT) mice. Adult female mice from these litters (7-8 wk old) were killed, and ring preparations of carotid and mesenteric arteries were mounted in a wire myograph to evaluate the passive and reactive vascular characteristics. Slope of the length-tension plot (a measure of vascular compliance) was increased, and optimal diameter (as calculated by Laplace equation) was decreased in NOS3(-/-KO) and NOS3(+/-mat) compared with NOS3(+/-pat) and NOS3(+/+WT) mice. Acetylcholine caused vasorelaxation in NOS3(+/-pat) and NOS3(+/+WT) and contraction in NOS3(-/-KO) and NOS3(+/-mat) mice. Responses to phenylephrine and Ca(2+) were increased in NOS3(-/-KO) and NOS3(+/-mat) compared with NOS3(+/-pat) and NOS3(+/+WT) mice. Relaxation to isoproterenol was decreased in NOS3(-/-KO) and NOS3(+/-mat) vs. NOS3(+/-pat) and NOS3(+/+WT) mice. Abnormalities in the passive and reactive in vitro vascular properties seen in NOS(+/-mat) that developed in a NOS3-deficient maternal/uterine environment compared with the genetically identical NOS3(+/-pat) mice that developed in a normal environment are the first direct evidence in support of a role for uterine environment in determining vascular function in later life. |
