Adrenal, kidney, and heart angiotensins in female murine ren-2 transfected hypertensive rats

Senanayake, P.; Smeby, Robert R.; Martins, Alberto Mesaque; Moriguchi, Atsushi; Kumagai, Hiroo; Ganten, Detlev; Brosnihan, K. Bridget

doi:10.1016/s0196-9781(98)00123-5

Cited by 29 publications

(25 citation statements)

References 33 publications

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“…otype were extracted for the measurement of Ang II and Ang I levels as described previously (40). The results are the average of duplicate pools Ϯ S.E.…”

Section: Methodsmentioning

confidence: 99%

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Kessler

Senanayake

Scheidemantel

et al. 2003

Journal of Biological Chemistry

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Angiotensin-converting enzyme (ACE) is expressed in many tissues, including vasculature and renal proximal tubules, and its genetic ablation in mice causes abnormal renal structure and functions, hypotension, and male sterility. To test the hypothesis that specific physiological functions of ACE are mediated by its expression in specific tissues, we generated different mouse strains, each expressing ACE in only one tissue. Here, we report the properties of two such strains of mice that express ACE either in vascular endothelial cells or in renal proximal tubules. Because of the natural cleavage secretion process, both groups also have ACE in the serum. Both groups were as healthy as wild-type mice, having normal kidney structure and fluid homeostasis, though males remained sterile, because they lack ACE expression in sperm. Despite equivalent serum ACE and angiotensin II levels and renal functions, only the group that expressed ACE in vascular endothelial cells had normal blood pressure. Expression of ACE, either in renal proximal tubules or in vasculature, is sufficient for maintaining normal kidney functions. However, for maintaining blood pressure, ACE must be expressed in vascular endothelial cells. These results also demonstrate that ACE-mediated blood pressure maintenance can be dissociated from its role in maintaining renal structure and functions.

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“…otype were extracted for the measurement of Ang II and Ang I levels as described previously (40). The results are the average of duplicate pools Ϯ S.E.…”

Section: Methodsmentioning

confidence: 99%

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Kessler

Senanayake

Scheidemantel

et al. 2003

Journal of Biological Chemistry

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“…25 Tissue homogenates were extracted using Sep-Pak columns, as described previously. [25][26][27] The eluate was divided for 3 radioimmunoassays [Ang I, Ang II, and Ang-(1-7)], and the solvent was evaporated. Ang I was measured using a modification of a commercially available Peninsula radioimmunoassay kit.…”

Section: Tissue Concentration Of Angiotensin Peptidesmentioning

confidence: 99%

Activation of Local Chorionic Villi Angiotensin II Levels But Not Angiotensin (1-7) in Preeclampsia

et al. 2008

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Abstract-The chorionic villi in the placenta are responsible for the regulation of fetal oxygen and nutrient transport.Although the peripheral renin-angiotensin system is activated during normal pregnancy, the regulation of the local chorionic villi renin-angiotensin system remains unknown. Therefore, placental chorionic villous tissue was collected from nulliparous third-trimester normotensive or preeclamptic subjects and was analyzed for angiotensin peptide content, angiotensinogen, renin, angiotensin-converting enzyme (ACE), ACE2, neprilysin, angiotensin II type 1 (AT 1 ), angiotensin II type 2, Mas receptor mRNAs, and angiotensin receptor density and subtype. Angiotensin II in chorionic villi was significantly higher in preeclamptic subjects, whereas angiotensin (1-7) was not different. Key Words: preeclampsia Ⅲ renin angiotensin system Ⅲ pregnancy Ⅲ placenta Ⅲ angiotensin receptors Ⅲ Mas receptor Ⅲ angiotensin (1-7) P reeclampsia, a hypertensive disorder of pregnancy, is clinically defined as maternal hypertension, proteinuria, and generalized edema occurring after the 20th week of gestation. Preeclampsia is the second leading cause of maternal mortality in the United States, affecting 7% to 10% of all pregnancies and contributing significantly to stillbirths and neonatal morbidity and mortality. 1 Thus, the prevention of preeclampsia would have a significant impact on maternal and neonatal outcome. Nevertheless, the pathophysiology of preeclampsia remains poorly understood. Although preeclampsia is often considered a multisystem disorder, one of the postulated pathological features of this disease is an impaired maternal uterine spiral artery remodeling. In preeclampsia, there is a decrease of embryonic trophoblast cell invasion of the uterine spiral arteries, which, in turn, prevents the diameter of these arteries from expanding and consequently leads to a reduction of blood flow into the placenta. 2,3 Without the remodeling of the uterine vasculature, the placenta becomes hypoxic as gestation advances, resulting in an oxygen deficiency within the tissue. The hypoxic placenta can then release factors into the maternal circulation that result in generalized endothelial dysfunction, vascular inflammation, and proteinuria. [3][4][5] Although several factors, including soluble fms-like tyrosine kinase 1 6 and soluble endoglin, 7 were discovered recently to play a role in the pathogenesis of preeclampsia, there are still many unanswered questions in the development of this disease.The renin-angiotensin system (RAS) is an important regulator of blood pressure, sodium, and fluid homeostasis and has been shown previously to play a role in preeclampsia. In normal pregnancy, estrogen causes an overexpression of the RAS by increasing both tissue and circulating levels of angiotensinogen 8,9 and renin. 10 -13 Consequently, plasma angiotensin (Ang) II is increased in association with the rise of angiotensinogen and plasma renin activity during gestation. 14,15 Normal pregnant women are resistant to the pressor effects...

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“…Prominent antihypertensive effects of Ang-(1-7) were demonstrated in experimental hypertensive models (32,33). Local regional angiotensin peptide levels (kidney and adrenal) are modulated by the estrous cycle, resulting in an increase in Ang I and/or its product Ang-(1-7) during estrus (34,35).…”

Section: Introductionmentioning

confidence: 99%

Enhanced expression of Ang-(1-7) during pregnancy

Brosnihan

Neves

Anton

et al. 2004

Braz J Med Biol Res

114

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Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

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Adrenal, kidney, and heart angiotensins in female murine ren-2 transfected hypertensive rats

Cited by 29 publications

References 33 publications

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Activation of Local Chorionic Villi Angiotensin II Levels But Not Angiotensin (1-7) in Preeclampsia

Enhanced expression of Ang-(1-7) during pregnancy

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