Networking Between Systemic Angiotensin II and Cardiac Mineralocorticoid Receptors

Blockade of central but not peripheral mineralocorticoid receptors, with the antimineralocorticoid RU-28318, reduces but does not suppress salt appetite aroused by sodium depletion in the rat. When central mineralocorticoid blockade is combined with captopril treatment to prevent formation of endogenous angiotensin II the appetite is completely suppressed. Suppression of the appetite occurred without changes in the animals' spontaneous ingestive behaviors, sodium excretion, or insulin-induced food intake. These results demonstrate that a synergy of angiotensin II and aldosterone is responsible for the expression of depletion-induced salt appetite in the rat.

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Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study

Journal of the American Heart Association ◽

10.1161/jaha.120.018716 ◽

2021 ◽

Author(s):

Rasmus Dreier ◽

Ulrik B. Andersen ◽

Julie L. Forman ◽

Majid Sheykhzade ◽

Martin Egfjord ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Crossover Study ◽

Plasma Concentrations ◽

Peripheral Resistance ◽

Cardiovascular Responses ◽

Mineralocorticoid Receptors ◽

Aldosterone Secretion ◽

Potassium Supplement ◽

Potassium Intake

Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone. Besides its well‐described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors‐independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium‐stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo‐controlled double‐blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure‐monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P =0.0002) and aldosterone (median [interquartile range], 440 [336–521] versus 237 [173–386] pmol/L; P <0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII‐stimulated aldosterone secretion ( P =0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII‐stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013‐004460‐66; URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02380157.

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Minireview: Aldosterone and Mineralocorticoid Receptors: Past, Present, and Future

Endocrinology ◽

10.1210/en.2010-0465 ◽

2010 ◽

Vol 151 (11) ◽

pp. 5098-5102 ◽

Cited By ~ 64

Author(s):

John W. Funder

Keyword(s):

Angiotensin Ii ◽

Primary Aldosteronism ◽

Mineralocorticoid Receptor ◽

Mineralocorticoid Receptors ◽

Receptor Signaling ◽

Receptor Agonists ◽

The Past ◽

Basic Biology ◽

Receptor Agonists And Antagonists

Although aldosterone was not isolated and chemically characterized until 1953, the mineralocorticoid action of certain steroids, notably deoxycorticosterone (DOC), had been recognized decades earlier. From 1953 until 1990 saw the establishment of the basic biology and clinical (patho)physiology of aldosterone as an epithelial sodium retaining hormone: its biosynthesis in the adrenal glomerulosa; control of its secretion by ACTH, angiotensin II, and plasma [K+]; its action via intracellular mineralocorticoid receptors to promote DNA-directed; RNA-mediated synthesis of proteins responsible for its epithelial effects; and the syndrome of primary aldosteronism, in which secretion of the hormone is relatively autonomous of its normal stimuli. The past 2 decades have been a major extension of our understanding of the pathophysiology of aldosterone and the complexities of mineralocorticoid receptor signaling in particular. This review concludes with a brief consideration of recent findings regarding hormone and receptor, agonists, and antagonists. In 1990 it might reasonably have been argued that we had the overarching framework for understanding the roles of aldosterone and mineralocorticoid receptors, with only the details to be filled in. Two decades later we still do not know the boundaries, and for every answer, two questions are springing up: truly the more we learn, the less we know.

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