Translational research goes both ways: lessons from clinical studies.

Translational research goes both ways: lessons from clinical studies. Research Abstract Details 

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Translational research goes both ways: lessons from clinical studies. Abstract Text:

1. It is currently assumed that translational research goes from benchtop to bedside; that aldosterone elevates blood pressure via its effects on salt and water homeostasis; that mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) share a common immediate ancestor; and that aldosterone plays a deleterious role in essential hypertension and heart failure. 2. Meta-analysis of clinical trials in essential hypertension, in which eplerenone was dose-titrated to attain diastolic blood pressure < 90 mmHg, showed no relationship between blood pressure response and electrolyte effects, as judged by change in plasma (K). 3. Reexamination of sequence data, and insights from the S810L MR mutant gene causing juvenile hypertension exacerbated by pregnancy, suggest that MR were the first to branch off the primordial ancestor for MR, GR, androgen receptors (AR) and progesterone receptors (PR). 4. In clinical trials of MR blockade in heart failure and essential hypertension baseline aldosterone levels are in the low to normal range and sodium status unremarkable. Under such circumstances cortisol appears to be responsible for MR activation, thus exculpating aldosterone in these conditions. 5. On the basis of these clinical studies, there is need to revisit the basic biology of aldosterone and MR as translational research very clearly goes both ways.

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Translational research goes both ways: lessons from clinical studies. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical and experimental pharmacology & physiolog

VOLUME: 35

Page Numbers: 526-9

Journal Abbreviation: Clin. Exp. Pharmacol. Physiol.

ISSN: 1440-1681

DAY: 29

MONTH: Apr

YEAR: 2008

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LANGUAGE: eng

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AFFILIATION: Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.

Country: Australia

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MEDLINETA: Clin Exp Pharmacol Physiol

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