Effect of a previous pregnancy on vascular function in endothelial nitric oxide synthase 3 knockout mice

Objective: Nitric oxide deficiency has been implicated in adverse pregnancy outcomes. Mice that lack endothelial nitric oxide synthase (NOS3) have abnormal in vitro vascular reactivity. Our objective was to assess the effect of a previous pregnancy on the abnormal vascular function of NOS3 knockout mice. Study Design: Carotid arteries from pregnant NOS3 knockout (NOS3^-/-KO) and wild-type control mice (NOS3^+/+WT) from first and second pregnancy were obtained for in vitro vascular reactivity studies. Vascular responses to cumulative concentrations of the vasoconstrictors phenylephrine, serotonin, and thromboxane and the vasorelaxants acetylcholine, sodium nitroprusside, and isoproterenol were determined. Results: In the first pregnancy, contractile responses were exaggerated in the knockout animals, compared with the wild-type animals. However, the second pregnancy in knockout animals was associated with normalization of responses to phenylephrine and serotonin and increased responses to the endothelium-independent relaxants. Conclusion: The vascular function of NOS3 knockout mice improves with subsequent pregnancy becoming comparable to wild-type animals.