Angiotensin II and aldosterone receptor binding in rat heart and kidney

Response to chronic angiotensin II or aldosterone administration

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Abstract

Angiotensin II (AII) and mineralocorticoid receptors (MRs) have been identified in the mammalian heart and kidney. Their response to chronic elevations in circulating AII or aldosterone (ALDO) (or both) is unknown in either primary or secondary hyperaldosteronism. Nonendothelial angiotensin-converting enzyme (ACE) activity has been found in the fibrous tissue response that involves intramyocardial coronary arteries and microscopic scarring. Whether this tissue ACE could affect AII receptors and MRs in the area of myocardial fibrosis is likewise unknown. To address these questions, we monitored AII and MR binding in the rat heart and kidney after chronic AII or ALDO infusion. All receptor and MR binding were localized by in vitro autoradiography with 125I-[Sar1, IIe8]-labeled AII and [1,2,6,7 3H]-labeled ALDO, respectively. To characterize AII receptor subtypes, a type I antagonist (DuP753) or type II antagonist (PD 123177) was used. Four experimental groups were examined: unoperated, untreated, age- and sex-matched controls; age- and sex-matched uninephrectomized control rats receiving a high sodium diet; animals that received AII (9 μg/hr sc) for 2, 4, 6, or 8 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/hr sc) for similar periods of time. We found that (1) AII receptors in heart and kidney were markedly reduced at all time points after AII infusion, (2) AII binding in heart and kidney was increased after ALDO infusion at all time points, (3) MR binding was unchanged in the heart while markedly decreased in the kidney after either AII or ALDO administration, (4) after uninephrectomy alone, progressive renal hypertrophy was observed together with an increase in MR binding after 6 and 8 weeks, and (5) AII and MR binding in the area of myocardial fibrosis was no different from normal myocardium in AII or ALDO-treated animals. Thus AII receptors in the rat heart and kidney and MR in the rat kidney are inversely related to circulating levels of AII and ALDO in keeping with receptor downregulatlon. Cardiac MRs, on the other hand, appear to be independent of plasma ALDO. Cardiac AII and MR binding is not related to high tissue ACE activity found in regions of fibrosis. Increased MR binding that appears over time in the hypertrophied unilateral kidney may be related to compensatory hyperfunction that is the result of high dietary sodium and that serves to maintain salt and water balance. (J Lab Clin Med1993;122:404-11).

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalThe Journal of Laboratory and Clinical Medicine
Volume122
Issue number4
StatePublished - Jan 1 1993
Externally publishedYes

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Mineralocorticoid Receptors
Angiotensin Receptors
Aldosterone
Angiotensin II
Rats
Kidney
Peptidyl-Dipeptidase A
Fibrosis
Sodium
Enzyme activity
Tissue
Nutrition
Animals
Rat control
Diet
Dietary Sodium
Hyperaldosteronism
Autoradiography
Hypertrophy
Cicatrix

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

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title = "Angiotensin II and aldosterone receptor binding in rat heart and kidney: Response to chronic angiotensin II or aldosterone administration",
abstract = "Angiotensin II (AII) and mineralocorticoid receptors (MRs) have been identified in the mammalian heart and kidney. Their response to chronic elevations in circulating AII or aldosterone (ALDO) (or both) is unknown in either primary or secondary hyperaldosteronism. Nonendothelial angiotensin-converting enzyme (ACE) activity has been found in the fibrous tissue response that involves intramyocardial coronary arteries and microscopic scarring. Whether this tissue ACE could affect AII receptors and MRs in the area of myocardial fibrosis is likewise unknown. To address these questions, we monitored AII and MR binding in the rat heart and kidney after chronic AII or ALDO infusion. All receptor and MR binding were localized by in vitro autoradiography with 125I-[Sar1, IIe8]-labeled AII and [1,2,6,7 3H]-labeled ALDO, respectively. To characterize AII receptor subtypes, a type I antagonist (DuP753) or type II antagonist (PD 123177) was used. Four experimental groups were examined: unoperated, untreated, age- and sex-matched controls; age- and sex-matched uninephrectomized control rats receiving a high sodium diet; animals that received AII (9 μg/hr sc) for 2, 4, 6, or 8 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/hr sc) for similar periods of time. We found that (1) AII receptors in heart and kidney were markedly reduced at all time points after AII infusion, (2) AII binding in heart and kidney was increased after ALDO infusion at all time points, (3) MR binding was unchanged in the heart while markedly decreased in the kidney after either AII or ALDO administration, (4) after uninephrectomy alone, progressive renal hypertrophy was observed together with an increase in MR binding after 6 and 8 weeks, and (5) AII and MR binding in the area of myocardial fibrosis was no different from normal myocardium in AII or ALDO-treated animals. Thus AII receptors in the rat heart and kidney and MR in the rat kidney are inversely related to circulating levels of AII and ALDO in keeping with receptor downregulatlon. Cardiac MRs, on the other hand, appear to be independent of plasma ALDO. Cardiac AII and MR binding is not related to high tissue ACE activity found in regions of fibrosis. Increased MR binding that appears over time in the hypertrophied unilateral kidney may be related to compensatory hyperfunction that is the result of high dietary sodium and that serves to maintain salt and water balance. (J Lab Clin Med1993;122:404-11).",
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T1 - Angiotensin II and aldosterone receptor binding in rat heart and kidney

T2 - Response to chronic angiotensin II or aldosterone administration

AU - Sun, Yao

AU - Weber, Karl

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Angiotensin II (AII) and mineralocorticoid receptors (MRs) have been identified in the mammalian heart and kidney. Their response to chronic elevations in circulating AII or aldosterone (ALDO) (or both) is unknown in either primary or secondary hyperaldosteronism. Nonendothelial angiotensin-converting enzyme (ACE) activity has been found in the fibrous tissue response that involves intramyocardial coronary arteries and microscopic scarring. Whether this tissue ACE could affect AII receptors and MRs in the area of myocardial fibrosis is likewise unknown. To address these questions, we monitored AII and MR binding in the rat heart and kidney after chronic AII or ALDO infusion. All receptor and MR binding were localized by in vitro autoradiography with 125I-[Sar1, IIe8]-labeled AII and [1,2,6,7 3H]-labeled ALDO, respectively. To characterize AII receptor subtypes, a type I antagonist (DuP753) or type II antagonist (PD 123177) was used. Four experimental groups were examined: unoperated, untreated, age- and sex-matched controls; age- and sex-matched uninephrectomized control rats receiving a high sodium diet; animals that received AII (9 μg/hr sc) for 2, 4, 6, or 8 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/hr sc) for similar periods of time. We found that (1) AII receptors in heart and kidney were markedly reduced at all time points after AII infusion, (2) AII binding in heart and kidney was increased after ALDO infusion at all time points, (3) MR binding was unchanged in the heart while markedly decreased in the kidney after either AII or ALDO administration, (4) after uninephrectomy alone, progressive renal hypertrophy was observed together with an increase in MR binding after 6 and 8 weeks, and (5) AII and MR binding in the area of myocardial fibrosis was no different from normal myocardium in AII or ALDO-treated animals. Thus AII receptors in the rat heart and kidney and MR in the rat kidney are inversely related to circulating levels of AII and ALDO in keeping with receptor downregulatlon. Cardiac MRs, on the other hand, appear to be independent of plasma ALDO. Cardiac AII and MR binding is not related to high tissue ACE activity found in regions of fibrosis. Increased MR binding that appears over time in the hypertrophied unilateral kidney may be related to compensatory hyperfunction that is the result of high dietary sodium and that serves to maintain salt and water balance. (J Lab Clin Med1993;122:404-11).

AB - Angiotensin II (AII) and mineralocorticoid receptors (MRs) have been identified in the mammalian heart and kidney. Their response to chronic elevations in circulating AII or aldosterone (ALDO) (or both) is unknown in either primary or secondary hyperaldosteronism. Nonendothelial angiotensin-converting enzyme (ACE) activity has been found in the fibrous tissue response that involves intramyocardial coronary arteries and microscopic scarring. Whether this tissue ACE could affect AII receptors and MRs in the area of myocardial fibrosis is likewise unknown. To address these questions, we monitored AII and MR binding in the rat heart and kidney after chronic AII or ALDO infusion. All receptor and MR binding were localized by in vitro autoradiography with 125I-[Sar1, IIe8]-labeled AII and [1,2,6,7 3H]-labeled ALDO, respectively. To characterize AII receptor subtypes, a type I antagonist (DuP753) or type II antagonist (PD 123177) was used. Four experimental groups were examined: unoperated, untreated, age- and sex-matched controls; age- and sex-matched uninephrectomized control rats receiving a high sodium diet; animals that received AII (9 μg/hr sc) for 2, 4, 6, or 8 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/hr sc) for similar periods of time. We found that (1) AII receptors in heart and kidney were markedly reduced at all time points after AII infusion, (2) AII binding in heart and kidney was increased after ALDO infusion at all time points, (3) MR binding was unchanged in the heart while markedly decreased in the kidney after either AII or ALDO administration, (4) after uninephrectomy alone, progressive renal hypertrophy was observed together with an increase in MR binding after 6 and 8 weeks, and (5) AII and MR binding in the area of myocardial fibrosis was no different from normal myocardium in AII or ALDO-treated animals. Thus AII receptors in the rat heart and kidney and MR in the rat kidney are inversely related to circulating levels of AII and ALDO in keeping with receptor downregulatlon. Cardiac MRs, on the other hand, appear to be independent of plasma ALDO. Cardiac AII and MR binding is not related to high tissue ACE activity found in regions of fibrosis. Increased MR binding that appears over time in the hypertrophied unilateral kidney may be related to compensatory hyperfunction that is the result of high dietary sodium and that serves to maintain salt and water balance. (J Lab Clin Med1993;122:404-11).

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