What question did this study set out to answer?

Determine whether circulating aldosterone crosses the blood-brain barrier to upregulate the hypothalamic renin-angiotensin system and elevate sympathetic drive during heart failure.

January 29, 2008HypertensionOpen Access

Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats With Heart Failure?

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Why the study?

Does intracerebroventricular RU28318 reduce hypothalamic RAS activity and sympathetic drive in rats with heart failure?

Population

Normal intact rats, adrenalectomized rats receiving subcutaneous infusions of aldosterone, rats with…

Comparison

Intracerebroventricular RU28318, a selective… vs Sham-operated controls and untreated heart…

Design

Preclinical

Follow-up

4 weeks

Authors

YYYang YuUniversity of Iowa SWShun‐Guang WeiUniversity of Iowa EGElise P. Gómez-SánchezIVI Murcia Clinic

Discussion

Member takes

Implication

Central MR blockade attenuates sympathetic drive in experimental HF; hypothesis-generating and leaves open human translation.

Key Points

Determine whether circulating aldosterone crosses the blood-brain barrier to upregulate the hypothalamic renin-angiotensin system and elevate sympathetic drive during heart failure.
Evaluated plasma and hypothalamic aldosterone levels across normal intact rats, adrenalectomized rats receiving subcutaneous aldosterone infusions, and rats with myocardial infarction-induced heart failure versus sham controls.
Treated heart failure rats with continuous intracerebroventricular infusion of the selective mineralocorticoid receptor antagonist RU28318 (1 µg/h) or vehicle for 4 weeks.
Assessed hypothalamic ACE and AT1 receptor mRNA and protein, paraventricular nucleus NADPH oxidase activity and superoxide production, neuronal activation, and circulating norepinephrine.
Heart failure rats exhibited proportional increases in plasma and hypothalamic aldosterone, accompanied by elevated hypothalamic ACE and AT1 receptor expression, increased paraventricular nucleus NADPH oxidase activity and superoxide generation, and elevated plasma norepinephrine.
Central mineralocorticoid receptor blockade with RU28318 substantially reduced hypothalamic ACE and AT1 receptor mRNA and protein, paraventricular nucleus superoxide generation, neuronal activation, and plasma norepinephrine in heart failure rats.
Central RU28318 administration did not alter circulating aldosterone concentrations or cortical ACE and AT1 receptor expression, confirming a targeted central hypothalamic mechanism.

Structured PICO

Does intracerebroventricular RU28318 reduce hypothalamic RAS activity and sympathetic drive in rats with heart failure?

Population

Normal intact rats, adrenalectomized rats receiving subcutaneous infusions of aldosterone, rats with ischemia-induced heart failure, and sham-operated controls

Intervention

Intracerebroventricular RU28318 (1 microg/h), a selective mineralocorticoid receptor antagonist, for 4 weeks

Comparator

Sham-operated controls and untreated heart failure state

Outcome

Hypothalamic angiotensin-converting enzyme and angiotensin type 1 receptor mRNA and protein expression, reduced nicotinamide-adenine dinucleotide phosphate-induced superoxide in the paraventricular nucleus, excitation of paraventricular nucleus neurons, and plasma norepinephrinesurrogate

Aldosterone of adrenal origin enters the hypothalamus in direct proportion to plasma levels and contributes to the upregulation of hypothalamic RAS activity and sympathetic drive in heart failure.

Cite This Study

Yu et al. (2008) studied this question.

synapsesocial.com/papers/6a81b2e128bb6950eb60fabf https://doi.org/10.1161/hypertensionaha.107.099796

Topics

Heart failure HFrEF treatment

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Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats With Heart Failure?

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Does Aldosterone Upregulate the Brain Renin-Angiotensin System in Rats With Heart Failure?

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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