Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background and Objectives

Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions.

Method

Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T ₃, and T ₄. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates.

Results

In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na ⁺ excretion, and K ⁺ excretion rates. Aliskiren was better at reducing the high blood pressure.

Conclusion

Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

Thyroid hormone regulation of metabolism.

Rashmi Mullur, Yan-Yun Liu, Gregory A Brent (2014)

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.

0 comments Cited 672 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

The Renin-Angiotensin Aldosterone System: Pathophysiological Role and Pharmacologic Inhibition

Steven A. Atlas (2007)

BACKGROUND: The renin-angiotensin aldosterone system (RAAS) is a hormonal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders. OBJECTIVES: To review the role of the RAAS in the development of hypertensive cardiovascular disease and related conditions and provide an overview of the classes of pharmacologic agents that inhibit this system. RESULTS: The RAAS is initiated by the regulated secretion of renin, the rate-limiting enzyme that catalyzes the hydrolysis of angiotensin (Ang) I from the N-terminus of angiotensinogen. Ang I is in turn hydrolyzed by angiotensin-converting enzyme (ACE ) to form Ang II, a potent vasoconstrictor and the primary active product of the RAAS. Recent evidence has suggested that other metabolites of Ang I and II may have biological activity, particularly in tissues. Development of agents that block the RAAS (e.g., beta blockers, ACE inhibitors [ACE Is], and angiotensin receptor blockers [ARBs]) began as a therapeutic strategy to treat hypertension. Preclinical and clinical studies have indicated important additional cardiovascular and renal therapeutic benefits of ACE Is and ARBs. However, blockade of the RAAS with these agents is incomplete. CONCLUSIONS: Therapeutic approaches that target more complete inhibition of the RAAS may offer additional clinical benefits for patients with cardiovascular and renal disorders. These approaches may include dual blockade using ACE Is and ARBs in combination, or new therapeutic modalities such as direct renin inhibition with aliskiren, recently approved for the treatment of hypertension.

0 comments Cited 150 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Thyroid dysfunction and kidney disease: An update.

Pedro Iglesias, Maria Auxiliadora Bajo, Rafael Selgas … (2017)

Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and sodium and water homeostasis. Hypothyroidism and hyperthyroidism affect renal function by direct renal effects as well as systemic hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been associated with increased serum creatinine and decreased glomerular filtration rate. The reverse effects have been reported in thyrotoxicosis. Most of renal manifestations of thyroid dysfunction are reversible with treatment. Kidney disease may also cause thyroid dysfunction by several mechanisms. Nephrotic syndrome has been associated to changes in serum thyroid hormone concentrations. Different forms of glomerulonephritis and tubulointerstitial disease may be linked to thyroid derangements. A high prevalence of thyroid hormone alteration has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent in chronic kidney disease patients. Subclinical hypothyroidism and low triiodothyronine syndrome are common features in patients with chronic kidney disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal transplantation recipients, exhibit thyroid hormone alterations and thyroid disease with higher frequency than that found in the general population. Drugs used in the therapy of thyroid disease may lead to renal complications and, similarly, drugs used in kidney disorders may be associated to thyroid alterations. Lastly, low thyroid hormones, especially low triiodothyronine levels, in patients with chronic kidney disease have been related to a higher risk of cardiovascular disease and all-cause mortality. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with thyroid and kidney disease.

0 comments Cited 91 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Susan A. S. Farhadi:

ORCID: https://orcid.org/0000-0003-1043-8519

Journal

Journal ID (nlm-ta): Int J Endocrinol

Journal ID (iso-abbrev): Int J Endocrinol

Journal ID (publisher-id): IJE

Title: International Journal of Endocrinology

Publisher: Hindawi

ISSN (Print): 1687-8337

ISSN (Electronic): 1687-8345

Publication date Collection: 2019

Publication date (Electronic): 18 July 2019

Volume: 2019

Electronic Location Identifier: 5960563

Affiliations

Department of Basic Sciences/ Pharmacology Unit, College of Medicine, Hawler Medical University, Erbil, Iraq

Author notes

Academic Editor: Giorgio Iervasi

Author information

Susan A. S. Farhadi https://orcid.org/0000-0003-1043-8519

Kawa F. Dizaye https://orcid.org/0000-0003-1739-8273

Article

DOI: 10.1155/2019/5960563

PMC ID: 6668533

PubMed ID: 31396276

SO-VID: 8a61c16f-bf92-4214-b09a-e49e70be3795

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 2 March 2019

Date revision received : 12 June 2019

Date accepted : 19 June 2019

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.