Increased sodium appetite and thirst in rat induced by the ingredients of liquorice, glycyrrhizic acid and glycyrrhetinic acid

Cooney, AS; Jt, Fitzsimons

doi:10.1016/0167-0115(96)00048-1

Cited by 16 publications

(9 citation statements)

References 11 publications

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“…This relatively small group of aldosterone-sensitive neurons is closely surrounded by a much larger population of neurons with the opposite pattern of activation (61), making traditional lesion or stimulation experiments in this region difficult to interpret. Nevertheless, the existence and characteristics of these neurons could help explain the paradoxical increases in salt intake in rats after systemic inhibition of HSD2 (31) and in a human with impaired HSD2 function (89), despite the concurrent sodium retention in each case, which should otherwise inhibit salt intake.…”

Section: Neurons Forming a Small Subpopulation Of The Nts Are Aldostementioning

confidence: 98%

Aldosterone in the brain

Geerling¹,

Loewy²

2009

American Journal of Physiology-Renal Physiology

163

151

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Pharmacological and physiological phenomena suggest that cells somewhere inside the central nervous system are responsive to aldosterone. Here, we present the fundamental physiological limitations for aldosterone action in the brain, including its limited blood-brain barrier penetration and its substantial competition from glucocorticoids. Recently, a small group of neurons with unusual sensitivity to circulating aldosterone were identified in the nucleus of the solitary tract. We review the discovery and characterization of these neurons, which express the enzyme 11beta-hydroxysteroid dehydrogenase type 2, and consider alternative proposals regarding sites and mechanisms for mineralocorticoid action within the brain.

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Section: Neurons Forming a Small Subpopulation Of The Nts Are Aldostementioning

confidence: 98%

Aldosterone in the brain

Geerling¹,

Loewy²

2009

American Journal of Physiology-Renal Physiology

163

151

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“…For example, HSD2 inhibition by glycyrrhetinic acid (the blood pressureincreasing constituent of licorice), allowing unrestricted MR activation by glucocorticoids, produces an adrenal steroiddependent increase in salt ingestion despite simultaneous overretention of sodium by the kidney (Cooney and Fitzsimons, 1996). Also, the HSD2 neurons lie immediately ventral to the area postrema, which innervates the NTS and exerts a powerful inhibitory influence on sodium appetite (Contreras and Stetson, 1981).…”

Section: Hsd2 Neurons As a Neuroanatomical Link To Sodium Appetitementioning

confidence: 99%

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

Geerling¹,

Engeland²,

Kawata³

et al. 2006

J. Neurosci.

135

187

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Sodium appetite can be enhanced by the adrenal steroid aldosterone via an unknown brain mechanism. A novel group of neurons in the nucleus tractus solitarius expresses the enzyme 11-␤-hydroxysteroid dehydrogenase type 2, which makes them selectively responsive to aldosterone. Their activation parallels sodium appetite in different paradigms of salt loss even in the absence of aldosterone. These unique aldosterone target neurons may represent a previously unrecognized central convergence point at which hormonal and neural signals can be integrated to drive sodium appetite.

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“…It is unclear why a volume balance is not achieved: 11␤HSD2-containing neurons in the nucleus of the solitary tract are stimulated by chronic hypovolemia, 34 and pharmacologic inhibition of the enzyme promotes thirst. 35 It may be that a fully operational renin-angiotensin system, suppressed in this model, is required to match precisely intake to output.…”

Section: Basic Research Wwwjasnorgmentioning

confidence: 99%

A Switch in the Mechanism of Hypertension in the Syndrome of Apparent Mineralocorticoid Excess

Bailey

Paterson

Hadoke

et al. 2008

Journal of the American Society of Nephrology

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The syndrome of apparent mineralocorticoid excess arises from nonfunctional mutations in 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), an enzyme that inactivates cortisol and confers aldosterone specificity on the mineralocorticoid receptor. Loss of 11␤HSD2 permits glucocorticoids to activate the mineralocorticoid receptor, and the hypertension in the syndrome is presumed to arise from volume expansion secondary to renal sodium retention. An 11␤HSD2 null mouse was generated on an inbred C57BL/6J genetic background, allowing survival to adulthood. 11␤HSD2 Ϫ/Ϫ mice had BP approximately 20 mmHg higher on average compared with wild-type mice but were volume contracted, not volume expanded as expected. Initially, impaired sodium excretion associated with increased activity of the epithelial sodium channel was observed. By 80 days of age, however, channel activity was abolished and 11␤HSD2 Ϫ/Ϫ mice lost salt. Despite the natriuresis, hypertension remained but was not attributable to intrinsic vascular dysfunction. Instead, urinary catecholamine levels in 11␤HSD2 Ϫ/Ϫ mice were double those in wild-type mice, and ␣1-adrenergic receptor blockade rescued the hypertensive phenotype, suggesting that vasoconstriction contributes to the sustained hypertension in this model. In summary, it is proposed that renal sodium retention remains a key event in apparent mineralocorticoid excess but that the accompanying hypertension changes from a renal to a vascular etiology over time. In 90% of hypertensive patients, the causal pathophysiology cannot be defined and, in 25%, BP fails to fall to target values with existing therapies. Improved understanding of pathogenesis is key to addressing this problem. Fundamental principles of BP homeostasis have been established through investigation of the rare Mendelian hypertensive disorders. These disorders result almost exclusively from mutations in genes encoding proteins influencing directly or indirectly sodium balance, 1 suggesting that altered renal salt homeostasis is a key factor in the misregulation of BP 2 The fine-tuning of sodium balance is achieved in the distal nephron, determined principally by the actions of aldosterone at the mineralocorticoid receptor (MR). In vitro, MR can be activated with equal potency by both mineralocorticoids and glucocorticoids. 3 In vivo, ligand access is determined by the enzyme 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), which catalyzes the rapid conversion of the active glucocorticoid cortisol (corticosterone in mice) to inert cortisone (11-dehydrocorticosterone), thereby

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Increased sodium appetite and thirst in rat induced by the ingredients of liquorice, glycyrrhizic acid and glycyrrhetinic acid

Cited by 16 publications

References 11 publications

Aldosterone in the brain

Aldosterone in the brain

Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite

A Switch in the Mechanism of Hypertension in the Syndrome of Apparent Mineralocorticoid Excess

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