Angiotensinogen gene expression in extrahepatic rat tissues: Application of a solution hybridization assay

Hellmann, W.; Suzuki, Fujio; Ohkubo, Hiroaki; Nakanishi, Shigetada; Ludwig, Gerald M.; Ganten, Detlev

doi:10.1007/bf00173408

Cited by 90 publications

(46 citation statements)

References 23 publications

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“…The detection of renin mRNA by in situ hybridization experiments in cells identified as gonadotropes (Deschepper et al 1986b) provides further evidence against an internalization of circulating RAS components in pituitary cells. Furthermore, AGT mRNA has also been detected in pituitary cell extracts, both by a solution hybridization assay (Hellmann et al 1988) and by RT-PCR (Sernia 1995).…”

Section: Discussionmentioning

confidence: 99%

Angiotensinogen, Prorenin, and Renin Are Co-localized in the Secretory Granules of All Glandular Cells of the Rat Anterior Pituitary: An Immunoultrastructural Study

Vila-Porcile

Corvol

1998

J Histochem Cytochem.

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SUMMARYIn addition to the circulating renin-angiotensin system (RAS), a local system has been postulated in the anterior pituitary because immunodetection of its components in various mammalian species. However, different cell types appear to be involved in different species, and there is no general consensus on the subcellular localization of prorenin, renin and angiotensinogen. In this ultrastructural study, we investigated and quantified the presence of these components using double or triple immunogold labeling methods, in all the immunologically identified glandular cell types of the rat anterior pituitary. In contrast to previous reports, all these components were identified not only in lactotropes and gonadotropes but also in somatotropes, corticotropes, and thyrotropes. The highest levels were detected in lactotropes and gonadotropes, and renin gave the greatest signal. Angiotensinogen, prorenin, and renin were co-localized in the secretory granules of all rat pituitary glandular cell types. The simultaneous detection of the substrate (angiotensinogen) and both its specific cleavage enzyme and its proenzyme within the same granule suggests intragranular processing of this component. Moreover, the localization of these three constituents in the secretory granules also suggests that, in the rat anterior pituitary, they follow the regulated secretory pathway. (J Histochem Cytochem 46:301-311, 1998)

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Section: Discussionmentioning

confidence: 99%

Angiotensinogen, Prorenin, and Renin Are Co-localized in the Secretory Granules of All Glandular Cells of the Rat Anterior Pituitary: An Immunoultrastructural Study

Vila-Porcile

Corvol

1998

J Histochem Cytochem.

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“…Hellmann et al 13 showed that angiotensinogen is expressed within the vessel wall. Naftilan and colleagues extended these observations by means of in situ hybridization.…”

Section: Discussionmentioning

confidence: 99%

Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.

et al. 1992

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Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3±9.5 versus 110.0±5.4 mm Hg, p<0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121±37 versus 39±12 fmol/30 min, n=7 each) and more angiotensin II (210±21 versus 62±12 fmol/30 min,/?<0.05, n-1 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation. (Hypertension 1992; 19:687-691) KEY WORDS • transgenic animals • renin • hind limb • converting enzyme inhibition R ecently, Mullins et al 1 were successful in producing rats transgenic for the mouse Ren-2 gene. These rats develop severe hypertension; however, they exhibit low, rather than elevated, plasma levels of renin and circulating angiotensin II (Ang II) despite the expression of the Ren-2 gene in several tissues.1 Nevertheless, the hypertension in these rats is readily responsive to low doses of angiotensin converting enzyme inhibitors.1 However, no evidence has been published that Ang II production is increased in these animals.During the past decade, attention has been drawn to local renin and angiotensin formation. Such systems have been described in the brain, heart, adrenal gland, and walls of blood vessels.2 " 5 However, the role of local Ang II production in the regulation of vascular tone remains unclear. We and others have used the isolated perfused rat hindquarter to demonstrate the activity of the vascular renin system by measuring local formation of angiotensin peptides. 5 -7 In the current study, we tested the hypothesis that rats transgenic for the mouse Ren-2 gene exhibit an increased formation of angiotensin peptides within the walls of blood vessels. We examined angiotensin release from isolated perfused rat hindquarters and demonstrated the expression of the transgene within the vessels of these rats. Our results provide direct evidence for increased blood...

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“…in the brush border membranes of the intestine (Ward et al, 1980). It has been demonstrated that angiotensinogen can be synthesized in extrahepatic tissues such as the aorta (Hellmann et al, 1988). In addition, renin was found to be synthesized in aortic smooth muscles (Re et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Demonstration of extrapulmonary activity of angiotensin converting enzyme in intact tissue preparations

Lembeck

Griesbacher

Eckhardt

1990

British J Pharmacology

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1 The activity of angiotensin converting enzyme (ACE) has been studied on functional parameters of intact isolated preparations of extrapulmonary tissues. The conversion of angiotensin I (A I) to angiotensin II (A II) and the cleavage of bradykinin (BK) were used as indicators of ACE activity. Captopril was employed as a specific inhibitor of ACE. 2 Captopril augmented the BK-induced contractions of the rat isolated uterus, the BK-and substance P-induced contractions of the guinea-pig ileum, and the BK-induced venoconstriction in the isolated perfused ear of the rabbit. Degradation of BK by ACE was calculated to be 52% in the rat uterus and 75% in the rabbit perfused ear. 3 Captopril inhibited the A I-induced contractions of the rat isolated colon, the A I-induced vasoconstriction in the isolated perfused ear of the rabbit and the rise in blood pressure induced by i.a. injections of A I in pithed rats. Conversion of A I to A II was calculated to be 13% in the rat colon and 26% in the rabbit perfused ear. 4 From estimations of the A II activity (bioassay on the rat colon) in the effluent of the perfused ear of the rabbit after injections of A I into the arterial inflow cannula it was calculated that approximately one tenth of A I was converted to A II during a single passage through the ear (less than 15 s). 5 The present experiments suggest that the high activity of ACE in endothelium of blood vessels of extrapulmonary tissues may provide an additional (endothelium-dependent) local vasoconstrictor mechanism by the rapid formation of A II and inactivation of BK. The ACE activity in non-vascular smooth muscles, other than those of blood vessels, may also affect the physiological functions of these tissues.

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Angiotensinogen gene expression in extrahepatic rat tissues: Application of a solution hybridization assay

Cited by 90 publications

References 23 publications

Angiotensinogen, Prorenin, and Renin Are Co-localized in the Secretory Granules of All Glandular Cells of the Rat Anterior Pituitary: An Immunoultrastructural Study

Angiotensinogen, Prorenin, and Renin Are Co-localized in the Secretory Granules of All Glandular Cells of the Rat Anterior Pituitary: An Immunoultrastructural Study

Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.

Demonstration of extrapulmonary activity of angiotensin converting enzyme in intact tissue preparations

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