Aldosterone: Renal Action and Physiological Effects

Johnston, Jermaine G.; Welch, Amanda; Cain, Brian D.; Sayeski, Peter P.; Gumz, Michelle L.; Wingo, Charles S.

doi:10.1002/cphy.c190043

Cited by 9 publications

(8 citation statements)

References 895 publications

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“…These results indicate that both Spi and Tet exhibit significant diuretic effects by excreting Na + and preserving K + . ALD is a mineralocorticoid hormone responsible for regulating the body fluids and ion exchange, and Preg is an important intermediate in the synthesis of this hormone ( Johnston et al, 2023 ). As shown in Figures 1H, I , the serum Preg and ALD levels were reduced in all Tet groups.…”

Section: Resultsmentioning

confidence: 99%

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension

Chu,

Yang,

et al. 2024

Front. Pharmacol.

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IntroductionTetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro.MethodsThe diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.ResultsTet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.DiscussionThis study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

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Section: Resultsmentioning

confidence: 99%

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension

Chu,

Yang,

et al. 2024

Front. Pharmacol.

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“…However, the clinical studies could not confirm significant involvement of glucocorticoids applied alone in fluid retention in critically ill patients and it has been postulated that effects of steroid hormones on water-electrolyte balance are mediated mainly by activation of mineralocorticoid receptors [210]. It is wells known that mineralocorticoids have a significant impact on electrolyte balance, especially on sodium and potassium turnover as well as on clearance of free water [211][212]. Moreover, components of the renin-angiotensin-aldosterone system (RAAS), acting in the hypothalamus are able to stimulate vasopressin secretion, thirst, and sodium appetite [213].…”

Section: Interaction Of Avp and Steroids In Regulation Of Water-elect...mentioning

confidence: 99%

Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases

Szczepańska-Sadowska,

Czarzasta,

Bogacki-Rychlik

et al. 2024

Preprint

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A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

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“…A relative excess of aldosterone contributes to about 20% of treatment-resistant hypertension and is thought to participate in low-renin hypertension, which affects up to 25% of patients with essential hypertension. 5 When aldosterone binds to the mineralocorticoid receptor, it stimulates the reabsorption of sodium by the distal kidney tubules and the colonic epithelium. The retention of sodium expands the circulating volume and contributes to an increase in BP by this volume expansion, often leading to a reduction in antihypertensive drug efficacy.…”

Section: Aldosterone and Bp Regulationmentioning

confidence: 99%

Section: Aldosterone and Bp Regulationmentioning

confidence: 99%