(Hypertension. 1995;25:170-173.)
© 1995 American Heart Association, Inc.
Articles |
Production of Aldosterone in Isolated Rat Blood Vessels
From the Second Department of Internal Medicine, School of Medicine, Kanazawa (Japan) University (Y.T., I.M., T.Y., K.I., H.H., R.T.), and the Division of Clinical Pharmacology, Mass Spectrometry Resource, School of Medicine, Vanderbilt University, Nashville, Tenn (I.A.B., F.-Y.H.).
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Abstract |
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Abstract Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9x10-10 mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.
Key Words: aldosterone • mesenteric artery • rats • adrenalectomy • angiotensin I–converting enzyme inhibitors • angiotensin II
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Introduction |
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Extra-adrenal steroid 21-hydroxylation and 11ß-hydroxylation occur in a variety of human tissues. In human adult and fetal extra-adrenal tissues, circulating progesterone is converted to deoxycorticosterone (DOC) or DOC sulfate.1 The extra-adrenal expression of steroid 21-hydroxylase and 11ß-hydroxylase by a benign testicular Leydig cell tumor has been reported.2 3 4 Recently, the physiological and pathophysiological importance of locally generated renin-angiotensin and angiotensin I (Ang I)–converting enzyme (ACE) in vascular tissue has been recognized.5 6 7 We undertook the present study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an ACE inhibitor, Ang II, or potassium on aldosterone production in vascular tissue.
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Methods |
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Male Wistar rats (Nippon Charles River) weighing 200 to 230 g were housed in metabolic cages with free access to tap water and normal rat chow (0.1 mmol/g sodium, 0.24 mmol/g potassium, Nippon Charles River). The first group of animals (n=7) was bilaterally adrenalectomized under ether anesthesia and allowed free access to 0.9% NaCl as drinking water at all times for 7 days. The control group (n=7) consisted of sham-operated animals drinking NaCl-free water. The second group of rats (n=14) was given 0.3 mg PO quinapril, a prodrug type of ACE inhibitor (Warner-Lambert Co Ltd), for 14 days. Age- and weight-matched Wistar rats receiving tap water to drink were used as controls. Completeness of adrenalectomy was confirmed at autopsy by visual inspection after experiments. Plasma concentrations of aldosterone and corticosterone were measured by radioimmunoassay after extraction with a Sep-Pak C18 cartridge (Waters Associates). Plasma renin activity (PRA) was measured using a commercial kit (Dinapot Co Ltd). With the animals under pentobarbital anesthesia (25 mg/kg IP), the mesenteric artery was immediately excised and prepared for perfusion following the methods originally described by McGregor8 with the minor modification previously reported by our laboratory.9 Briefly, the arteries were perfused with Krebs-Ringer solution, pH 7.4, prewarmed, and oxygenated with a 95% O2/5% CO2 gas mixture at a constant flow rate of 4 mL/min. The perfusion pressure was constantly monitored by a pressure transducer connected to a polygraph (RM 600, Nihon-Koden) and recorded. After 30 minutes of equilibration, the perfusate was collected for 4 hours. The perfusate was extracted with a Sep-Pak C18 cartridge and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system using methanol/water (40%/100%) for 60 minutes as the mobile phase at a flow rate of 1.5 mL/min. The retention times of 18-hydroxycorticosterone, aldosterone, corticosterone, deoxycorticosterone, progesterone, and pregnenolone were 35, 32, 43, 49, 55, and 59 minutes, respectively. The fraction corresponding to synthetic aldosterone was collected and analyzed by gas chromatography/mass spectrometry (GC/MS). The applied GC temperature was 90°C during injection, then 180° to 290°C at 4°/min. The MS conditions were electroimpact ionization (70 eV) and a linear up scan m/z of 70 to 750 in a 2-second scanning period. After derivatization as described,10 the samples were dissolved in hexane and injected into a GC/MS system.
The aldosterone concentration in the perfusate from the adrenalectomized rats (n=7), sham-operated rats (n=7), rats treated with the ACE inhibitor (n=7), and controls was measured using radioimmunoassay after HPLC separation. Mesenteric arteries from Wistar rats (n=14) were perfused with Krebs-Ringer solution. The concentration of 1.9x10-10 mol/L Ang II was administered by continuous injection for 4 hours. The Krebs-Ringer solution containing 6 mmol/L potassium was perfused for 4 hours. The aldosterone concentration in the perfusate was measured by the same methods as described above. After the experiments of perfusate, the mesenteric artery was homogenized in 10 mL Krebs-Ringer buffer solution in a tissue grinder. Protein assay was done by the method of Bradford.11
After rats were decapitated, mesenteric arteries from rats treated with the ACE inhibitor (n=7) and control rats (n=5) were removed and fixed in Duboscq-Brazil solution.12 After dehydration, those mesenteric arteries were embedded in paraffin and cut into 5-µm transverse sections and stained with orcein. The protocol was approved by the Animal Research Committee of this institution.
The time course of aldosterone production in isolated perfused mesenteric preparations was examined up to 5 hours. Aldosterone production was found to be stable up to 4 hours (data not shown).
Data are expressed as mean±SEM. Statistical analysis of the results was done by Wilcoxon's unpaired t test, with a value of P<.05 accepted as statistically significant.
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Results |
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Fig 1 shows the HPLC elution profile of immunoreactive aldosterone in the perfusate of mesenteric arteries. Five peaks with aldosterone-like immunoreactivity were detected. The antibody of aldosterone has cross-reactivity with other steroids such as 19-noraldosterone, 18-hydroxydeoxycorticosterone, and 19-hydroxyaldosterone. One aliquot with a retention time of 32 minutes (the retention time of aldosterone) was injected into the GC/MS system. The top portion of Fig 2 shows the mass spectra obtained after the injection of synthetic aldosterone. As shown in the bottom portion of Fig 2, the mass spectra of aldosterone isolated from rat mesenteric arteries were identical to those of synthetic aldosterone. The immunoreactive peak of corticosterone was detected in the fraction with a retention time of 43 minutes (data not shown).
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The sensitivity of the assay of aldosterone or corticosterone was 30 fmol. The overall recovery was 70%, interassay variation was 13.5%, and intra-assay variation was 9.5% for aldosterone in the HPLC system.
The Table shows the data for PRA, plasma aldosterone concentration, and plasma corticosterone concentration in each experimental rat group. PRA was significantly higher in adrenalectomized rats than in sham-operated rats and lower in rats treated with the ACE inhibitor than in controls. In adrenalectomized rats, plasma aldosterone and corticosterone were not detected by radioimmunoassay when 1 mL plasma was used. Rats treated with the ACE inhibitor showed significantly lower plasma aldosterone concentrations than controls (P<.05). There were no significant differences in plasma corticosterone levels between rats treated with the ACE inhibitor and control rats. Apparently, the ACE inhibitor does not affect the activities of the enzymes involved in biosynthesis of corticosterone.
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Fig 3 shows the results of aldosterone production from mesenteric artery in each experimental rat group. Aldosterone production in rats treated with the ACE inhibitor was significantly reduced compared with that of controls (0.36±0.04 versus 0.70±0.14 pmol/mg protein per hour, P<.05). Adrenalectomy significantly increased aldosterone production compared with sham-operated rats (0.90±0.10 versus 0.71±0.12 pmol/mg protein per hour, P<.05).
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Ang II (1.9x10-10 mol/L) and potassium (6.0 mmol/L) significantly increased aldosterone production in the mesenteric artery from a basal value of 0.70±0.14 pmol/mg protein per hour to 1.1±0.20 and 1.0±0.15 pmol/mg protein per hour, respectively (P<.05).
There were no significant differences of mesenteric artery media thickness between rats treated with the ACE inhibitor and controls.
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Discussion |
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In this study we present evidence for aldosterone synthesis in vascular tissue. Extra-adrenal steroid synthesis has been widely reported. Steroid 21-hydroxylation occurs in a wide variety of human adult and fetal extra-adrenal tissues, which take up circulating progesterone and convert it to DOC or DOC sulfate. Namiki et al13 reported the production of DOC, corticosterone, and cortisol and also the expression of P-450C21 and P-450C11 mRNA in Leydig cell tumors, as well as the presence of steroid 21-hydroxylase activity in testicular tissues adjacent to Leydig cell tumors. Recently, aldosterone synthase cytochrome P-450 (P-450aldo) induced in sodium-deplete, potassium-replete rat adrenal cortex has been isolated, and it has been demonstrated that the P-450aldo catalyzes successive monooxygenation reactions of DOC to produce aldosterone as a final product, whereas rat P-45011ß does not sufficiently catalyze the reactions to form aldosterone.14 15 In addition, cDNAs for rat P-450 distinct from those of rat P-45011ß have been isolated.16 Imai et al15 reported that P-450aldo mRNA in the adrenal gland is detectable only by Ang II stimulation. Curnow et al17 demonstrated that P-450aldo mRNA in the adrenal gland is detectable using a polymerase chain reaction technique. Yamamoto et al (personal communication) detected P-450aldo mRNA in cultured vascular endothelial cells using a reverse transcriptase–polymerase chain reaction method. We confirmed the production of aldosterone in cultured rat aortic endothelial cells using the same methods (data not shown). These results support the hypothesis that aldosterone in the perfusate does not reflect uptake from plasma, in addition to the results that aldosterone in the perfusate from adrenalectomized rats, whose plasma aldosterone level is not detectable, is increased. Corticosterone-like immunoreactivity was detected in the perfusate. We detected the radioactive peak of progesterone, deoxycorticosterone, corticosterone, 18-hydroxycorticosterone, and aldosterone in the perfusate after perfusing the mesenteric artery with Krebs-Ringer solution containing [14C]pregnenolone (data not shown). These results indicate that precursors of aldosterone may exist in the vasculature.
The amount of aldosterone produced in the mesenteric artery is very small compared with plasma or adrenal aldosterone. However, vascular endothelial cells are shown to possess aldosterone synthase and produce aldosterone. There is a possibility that systemic vessels are able to locally produce aldosterone. There is increasing evidence that the tissue renin-angiotensin system, which functions on the autocrine-paracrine level,18 is important for cardiovascular regulation.19 20 Mineralocorticoid receptors exist in the vasculature.21 22 Brilla et al23 reported that Ang II stimulated aldosterone synthesis in cultured bovine aortic endothelial cells and that the renin-angiotensin-aldosterone system exists in vascular tissues.
We previously reported that Ang II is produced independently of the systemic renin-angiotensin system.24 The amount of Ang II produced was reduced to approximately 50% of the control value after the administration of an ACE inhibitor, similar to the extent of aldosterone inhibition observed in this study after treatment with quinapril. In adrenalectomized rats, PRA was high and plasma aldosterone was not detected, but the aldosterone concentration in the perfusate was increased compared with that in sham-operated controls. Ang II and potassium increased aldosterone production in the mesenteric artery. Taken together, these results show that renin-angiotensin and aldosterone may be synthesized and regulated in a closely linked manner in the vascular system. Ang II and aldosterone may have cell-signaling paracrine functions18 25 that contribute to cardiovascular structure during normal growth26 27 and development and in pathological conditions.25 Further study is necessary to clarify the pathophysiological role of vascular aldosterone.
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Footnotes |
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Reprint requests to Isamu Miyamori, MD, Second Department of Internal Medicine, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920 Japan.
Received March 7, 1994; first decision April 13, 1994; accepted October 19, 1994.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Casey ML, MacDonald PC. Extraadrenal formation of a mineralocorticoid: deoxycorticosterone and deoxycorticosterone sulfate bio-synthesis and metabolism. Endocr Rev. 1982;3:396-403.
2. Mellon SH, Miller WL. Extraadrenal steroid 21-hydroxylation is not mediated by P-450c21. J Clin Invest. 1989;84:1497-1502.
3.
Blumberg-Tick J, Boudou P, Nahoul K, Schaison G. Testicular
tumors in congenital adrenal hyperplasia: steroid measurement from
adrenal and spermatic veins. J Clin Endocrinol Metab. 1991;73:1129-1133.
4.
Solish SB, Goldsmith MA, Voutilainen GR, Miller W. Molecular
characterization of a Leydig cell tumor presenting as congenital
adrenal hyperplasia. J Clin Endocrinol Metab. 1989;69:1148-1152.
5. Okamura T, Aimi Y, Kimura H, Murakami K, Toda N. Existence of renin in the endothelium of human artery. J Hypertens. 1992;10:49-53. [Medline] [Order article via Infotrieve]
6.
Rakugi H, Jacob HJ, Krieger LE, Ingelfinger JR, Pratt RE.
Vascular injury induces angiotensinogen gene expression in the media
and neointima. Circulation. 1993;87:283-290.
7.
King SJ, Oparil S. Converting-enzyme inhibitors increase
converting-enzyme mRNA and activity in endothelial cells. Am J
Physiol. 1992;263:C743-C749.
8. McGregor DD. The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol (Lond). 1965;117:21-30.
9. Takeda Y, Miyamori I, Yoneda T, Takeda R. Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats. Life Sci. 1991;48:2553-2556. [Medline] [Order article via Infotrieve]
10. Takeda Y, Kathalina B, Iwuanyanwu T, Lewicka S, Vecsei P, Abdelhamid S, Harnik M. Urinary 18,19-dihydroxycorticosterone excretion in patients with primary and secondary aldosteronism. Steroids. 1991;56:566-570. [Medline] [Order article via Infotrieve]
11. Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle protein-dye binding. Anal Biochem. 1976;72:248-252. [Medline] [Order article via Infotrieve]
12.
Levy BI, Michel JB, Salzmann JL, Aziri M, Poitevin P, Safer
ME, Camilleri JP. Effect of chronic inhibition of converting enzyme on
mechanical and structural properties of arteries in rat renovascular
hypertension. Circ Res. 1988;63:227-239.
13. Namiki M, Koh E, Meguro N, Kondoh N, Sonada T. Exrtaadrenal expression of steroid 21-hydroxylase and 11ß-hydroxylase by a benign testicular Leydig cell tumor. J Steroid Biochem Mol Biol. 1991;39:897-901. [Medline] [Order article via Infotrieve]
14. Lauber M, Boni-Schnetzler M, Muller J. Potassium raises cytochrome P-450 mRNA level in zona glomerulosa of rat adrenals. Mol Cell Endocrinol. 1990;72:159-166. [Medline] [Order article via Infotrieve]
15.
Imai M, Ogishima T, Shimada H, Ishimura Y. Effect of dietary
sodium restriction on mRNA for aldosterone synthase cytochrome P-450 in
rat adrenals. J Biochem. 1992;111:440-443.
16. Imai M, Shimada H, Okada Y, Ogishima T, Ishmura Y. Molecular cloning of a cDNA encoding aldosterone synthase cytochrome P-450 in rat adrenal cortex. FEBS Lett. 1990;263:299-302. [Medline] [Order article via Infotrieve]
17. Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL, White PC. The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol. 1991;10:1513-1522.
18. Dzau VJ. Circulating versus local renin-angiotensin-system in cardiovascular homeostasis. Circulation. 1988;77(suppl I):I-4-I-13.
19. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest. 1977;79:1-6.
20. Paul M, Wagner J, Dzau VJ. Gene expression of the renin-angiotensin system in human tissues. J Clin Invest. 1993;91:2058-2064.
21. Kornel L, Rafelson ME, Hayashi T, Kanamarlapudi N, Anderson KM. Arterial receptors for adrenal steroids and transport of electrolytes in vascular smooth muscle. Clin Physiol Biochem. 1988;6:188-200. [Medline] [Order article via Infotrieve]
22.
Funder JW, Pearce PT, Smith R, Campbell J. Vascular type I
aldosterone binding sites are physiological mineralocorticoid
receptors. Endocrinology. 1989;125:2224-2226.
23. Brilla CG, Myers ZG, Weber KT. Angiotensin II-mediated aldosterone synthesis in cultured bovine aortic cells. J Hypertens. 1992;10:S75.
24. Miyamori I, Matsubara T, Takeda Y, Koshida H, Soma R, Takeda R. Angiotensin II generation in mesenteric arteries in rats: effects of nephrectomy, deoxycorticosterone and dexamethasone. Endocrinol Jpn. 1990;37:9-17. [Medline] [Order article via Infotrieve]
25.
Weber KT, Brilla CG. Pathological hypertrophy and cardiac
interstitium: fibrosis and renin-angiotensin-aldosterone system.
Circulation. 1991;83:1849-1865.
26. Baker KM, Booz GW, Dostal DE. Cardiac actions of angiotensin II: role of an intracardiac renin-angiotensin system. Annu Rev Physiol. 1992;54:227-241. [Medline] [Order article via Infotrieve]
27.
Keeley FW, Elmoselhi A, Leenan FHH. Enalapril suppresses
normal accumulation of elastin and collagen in cardiovascular tissues
of growing rats. Am J Physiol. 1992;262:H1013-H1021.
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Y. Takeda, I. Miyamori, S. Inaba, K. Furukawa, H. Hatakeyama, T. Yoneda, H. Mabuchi, and R. Takeda Vascular Aldosterone in Genetically Hypertensive Rats Hypertension, January 1, 1997; 29(1): 45 - 48. [Abstract] [Full Text]
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M. E. Ullian, D. J. Hazen-Martin, L. G. Walsh, R. K. Davda, and B. M. Egan Carbenoxolone Damages Endothelium and Enhances Vasoconstrictor Action in Aortic Rings Hypertension, June 1, 1996; 27(6): 1346 - 1352. [Abstract] [Full Text]
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