Adrenal Renin: A Possible Regulator of Aldosterone Production

Doi, Yutaka; Atarashi, Keiichiro; Franco‐Saenz, Roberto; Mulrow, Patrick J.

doi:10.3109/10641968309048845

Cited by 59 publications

(35 citation statements)

References 7 publications

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“…10 - 11 Recently, we showed that almost all of renin mRNA was in the adrenal zona glomerulosa with very little in the zona fasciculatareticularis and that the renin mRNA increased after sodium depletion in the rat. 17 These observations suggest that adrenal renin synthesized in glomerulosa cells may be a possible regulator of aldosterone secretion.…”

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confidence: 99%

Role of the adrenal renin-angiotensin system on adrenocorticotropic hormone- and potassium-stimulated aldosterone production by rat adrenal glomerulosa cells in monolayer culture.

et al. 1990

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The rat zona glomerulosa has a renin-angiotensin system that appears to function as an autocrine or paracrine system in the regulation of aldosterone production. To further investigate dynamic changes of production of renin and aldosterone in vitro we developed a primary monolayer culture of rat adrenal glomerulosa cells in serum-free medium. Collagenase-dispersed glomerulosa cells were incubated in PFMR-4 medium containing 10% fetal calf serum for 48 hours; the medium was then replaced with serum-free PFMR-4 medium. The cell viability and the aldosterone secretion were stable over the additional 48 hours in the serum-free control medium. After incubation for 24 hours in the serum-free medium, the cells were exposed to high K + or adrenocorticotropic hormone (ACTH) for another 24 hours. ACTH stimulated aldosterone secretion, and this increased secretion was associated with an increase in renin activity ( demonstrated. These observations provide evidence that the renin found in the adrenal is, at least in part, synthesized locally. Our laboratory also has shown that adrenal renin increases after a low sodium or high potassium diet and after nephrectomy and that there is a positive correlation between adrenal renin and adrenal aldosterone concentration. -11 Recently, we showed that almost all of renin mRNA was in the adrenal zona glomerulosa with very little in the zona fasciculatareticularis and that the renin mRNA increased after sodium depletion in the rat. 17 These observations suggest that adrenal renin synthesized in glomerulosa cells may be a possible regulator of aldosterone secretion.Recently, our laboratory investigated the production of renin, angiotensin II, and aldosterone in rat adrenal capsular explant cultures in serum-free me-

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Role of the adrenal renin-angiotensin system on adrenocorticotropic hormone- and potassium-stimulated aldosterone production by rat adrenal glomerulosa cells in monolayer culture.

et al. 1990

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“…In the past decade, several studies conducted on animals found evidence for a complete RAS within various tissues, suggesting that locally generated Ang II may act as an autocrine or paracrine mediator that might be independently regulated from circulating RAS. 1 - 2 In the adrenals, local production of Ang II and angiotensin III (Ang III) may stimulate mineralocorticoid synthesis and secretion 3 and growth of adrenal cells 4 and may have an important role in the pathogenesis of high blood pressure, as suggested by studies on transgenic rats with high adrenal renin expression. 5 Many studies reported the presence of some RAS components in the adrenals of various animal species.…”

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Local renin-angiotensin system in human adrenals and aldosteronomas.

et al. 1992

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The local renin-angiotensin system may regulate adrenal cell growth and function. Angiotensinogen, renin, and angiotensin converting enzyme gene expression were studied in four normal adrenal glands (removed from patients with renal carcinomas) and five aldosterone-secreting adenomas. Northern blot analysis showed expression of angiotensinogen messenger RNA (mRNA) in normal adrenals at levels approximately 35 -fold lower than liver and sixfold lower than kidney. Similar angiotensinogen mRNA levels were present in two aldosteronomas, whereas a third had levels approximately 50% of those found in kidney. Renin mRNA was detectable in most normal adrenals and in three adenomas, one of which had relatively high renin mRNA levels. Angiotensin converting enzyme gene was expressed in adrenal tissue and in three adenomas. Portions from these normal adrenals and two of these aldosteronomas, as well as samples from two other adrenals and three aldosteronomas, were also studied in an in vitro supervision system coupled with active renin radioimmunometric assay, angiotensin II/HI, and aldosterone radioimmunoassay. Total amounts of active renin and angiotensin II/IH released from normal adrenals during 270 minutes of supervision were higher than the amounts released from aldosteronomas (312±35 versus 187+43 and 823±100 versus 436±55 pg/100 mg tissue, respectively; mean±SEM, p<0.05), whereas aldosterone release from the adenomatous tissue was approximately threefold higher (320±21 versus 115±18 ng/100 mg tissue; mean±SEM, p<0.01). Total amounts of active renin and angiotensin II/IH released by normal or adenomatous adrenal samples exceeded threefold to fourfold the amounts extracted from similar samples of the same surgical specimen. These findings provide evidence for a local renin-angiotensin system in human adrenals and in at least some aldosteronomas. (Hypertension 1992;19:702-707) KEY WORDS • angiotensinogen • renin • angiotensin II • adrenal glands • aldosterone • human studies • angiotensin converting enzyme T he renin-angiotensin system (RAS) has been considered as an endocrine system whose components are synthesized by different organs and interact in the circulation to generate the active peptide angiotensin II (Ang II), which then reaches target cells. In the past decade, several studies conducted on animals found evidence for a complete RAS within various tissues, suggesting that locally generated Ang II may act as an autocrine or paracrine mediator that might be independently regulated from circulating RAS.

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“…On the other hand, recent biochemical and immunological studies revealed that renin exists in the adrenal gland of various mammalian species (1)(2)(3)(4)(5). It was also demonstrated that this adrenal renin is primarily located in the zona glomerulosa cells rather than the fasciculata or medullary cells (6,7). Further, the adrenal renin has been reported to increase markedly after high potassium loading or after nephrectomy (7)(8)(9), when plasma renin activity was at undetectable levels.…”

Section: Introductionmentioning

confidence: 99%

Presence of renin secretory granules in rat adrenal gland and stimulation of renin secretion by angiotensin II but not by adrenocorticotropin.

Mizuno¹,

Hoffman²,

McKenzie³

et al. 1988

J. Clin. Invest.

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Renin has been identified biochemically and immunohistochemically in the adrenal gland. We examined the subcellular distribution and behavior of adrenal renin. By differential centrifugation of adrenal capsules, we found renin mainly in mitochondrial fractions. By Percoll density gradient centrifugation of this fraction, dense granules were separated from mitochondria and microsomes. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of the intact rat. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin in these granules. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 46 times faster than from the organs of intact animals. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the secretion was stimulated by potassium chloride (10 mM) or angiotensin II (10--10-M) but not by ACI'H (10-9-10-7 M), suggesting stimulation by intracellular calcium. These results provide evidence that the adrenal synthesizes renin, stores it in specific secretory granules and secretes it in a regulated manner.

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Adrenal Renin: A Possible Regulator of Aldosterone Production

Cited by 59 publications

References 7 publications

Role of the adrenal renin-angiotensin system on adrenocorticotropic hormone- and potassium-stimulated aldosterone production by rat adrenal glomerulosa cells in monolayer culture.

Role of the adrenal renin-angiotensin system on adrenocorticotropic hormone- and potassium-stimulated aldosterone production by rat adrenal glomerulosa cells in monolayer culture.

Local renin-angiotensin system in human adrenals and aldosteronomas.

Presence of renin secretory granules in rat adrenal gland and stimulation of renin secretion by angiotensin II but not by adrenocorticotropin.

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