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Local concentrations of the vasopressor peptide, angiotensin II (AngII), depend upon the balance between synthesis and degradation. Previous studies of blood pressure (BP) regulation have focused primarily on the generation of AngII and its receptors, and less attention has been devoted to angiotensin degradation. Aminopeptidase A (APA, EC 3.4.11.7) is responsible for the N-terminal cleavage of AngII, a hydrolytic event that serves as a rate-limiting step in angiotensin degradation. To evaluate the physiological role of APA, we examined BP homeostasis in APA-deficient mice. We measured basal BP and BP with continuous infusion of AngII in APA mutant mice by tail-cuff method. We also evaluated the development and histology of AngII-targeted organs as well as urine excretion in these mice. Homozygous APA mutant mice were found to have elevated basal systolic BP when compared with heterozygous mutant and wild-type littermate mice. Infusion of AngII led to an enhanced systolic BP response in the APA-deficient mice. Despite the sustained elevation of BP in APA knockout mice, neither their renal and cardiac sizes nor their histological appearances were not different from control mice. Moreover, the volume, osmolality, and electrolyte content of the urine were normal in APA-deficient mice. APA deficiency increased baseline BP and enhanced the hypertensive response to increased levels of AngII. These findings indicate a physiological role for APA in lowering BP and offer novel insight into the mechanisms for developing hypertension.

Abstract-To clarify the vascular endothelial function in pregnant women with hypertensive disorders, we assessed the flow-mediated vasodilation in the radial artery and compared it with plasma fibronectin levels. We determined flow-mediated vasodilation by measuring the change in radial artery diameter during hyperemia in 58 normal pregnant women, 22 preeclamptic pregnant women, and 15 pregnant women with chronic hypertension. In 41 of the 95 pregnant women, we measured the plasma fibronectin levels. Flow-mediated vasodilation in preeclamptic women was significantly less than that in normal pregnant women (PϽ0.001). In chronic hypertensive women, flow-mediated vasodilation was significantly less than that in normal pregnant women (PϽ0.001) but more than that in preeclamptic women (PϽ0.001). Flow-mediated vasodilation showed significant negative correlation with plasma fibronectin levels (PϽ0. 001, rϭ0.73 Key Words: endothelium Ⅲ vasodilation Ⅲ preeclampsia Ⅲ hypertension, pregnancy Ⅲ fibronectins R ecent evidence suggests that vascular endothelial dysfunction might play an important role in the pathogenesis of preeclampsia. 1,2 There are several suggested methods for assessment of the endothelial damage, including the evaluation of endothelial cell-derived biochemical markers. Endothelium-related serum factors such as cellular fibronectin and the von Willebrand factor have been shown to be abnormal in preeclampsia. [3][4][5] Another method is the assessment of endotheliumdependent vascular relaxing function. An important functional consequence of endothelial dysfunction is the inability to release endothelium-derived relaxing factor (EDRF). 6 EDRF is released in response to various pharmacological and physiological stimuli 7,8 and results in increased blood flow. Under physiological conditions, increased blood flow subsequent to the release from temporal occlusion of the peripheral artery causes vasodilation, which is called reactive hyperemia. 8 With high-resolution ultrasound, it is possible to objectively observe the vascular changes associated with reactive hyperemia. 9 -11 To clarify the endothelial function in pregnancy complicated with hypertensive disorders, we noninvasively assessed the flow-mediated vasodilation in the radial artery with a recently developed 30-MHz mechanical linear probe. Previously, we reported flow-mediated vasodilation in smaller number of pregnant subjects. 12 In our current report, we measured plasma fibronectin level, one of the endothelial cell-injury markers, and determined the relationship between vasodilation and fibronectin level. MethodsWe examined a total of 95 Japanese women, including 58 normal pregnant women, 22 pregnant women with preeclampsia, and 15 pregnant women with chronic hypertension. The diagnosis of preeclampsia and chronic hypertension was established on the basis of the criteria of the Committee on Terminology of the American Collage of Obstetricians and Gynecologists. 13 All the subjects were nonsmokers and received no antihypertensive agents before the...

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