Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism.
Adrenomedullin (AM) is located in the zona glomerulosa of the adrenal cortex and is considered to suppress aldosterone release. To determine the effect of AM in primary aldosteronism (PA), we infused AM (2.5 pmol kg(-1) min(-1)) for 27 h, followed by a 15-h recovery period, in a control group (essential hypertensives with plasma aldosterone levels <or=100 pg ml(-1), n=7) and in a PA group (n=5). The control group was also infused with vehicle. Hemodynamic, hormonal, oxidative and inflammatory responses were studied. AM infusion caused similar and steady decreases in blood pressure and several markers for arteriosclerosis (for example, pulse wave velocity) in both groups. Interestingly, AM infusion suppressed aldosterone release to values within the normal range in the PA group (300.0+/-58.4 to 111.6+/-13.5 pg ml(-1), P<0.01). In the control group, aldosterone release suppression was significant but limited (81.7+/-9.1 to 47.9+/-9.9 pg ml(-1), P<0.01). The adrenocorticotropic hormone-cortisol system was not changed by AM infusion. Brain natriuretic peptide was cumulatively increased by prolonged AM infusion in both groups, probably because of cardiac overload. AM did not affect oxidative markers. In addition, a mild but significant increase in C-reactive protein (CRP) mediated by interleukin-6 was observed during AM infusion in every participant, without exception. This pathway might participate in CRP elevation in cardiovascular disease. In summary, AM seems to have an essential role in the suppression of aldosterone release in PA. AM may be an important modulator in PA, and intermediate-term (3 h) AM infusion could be used as an alternative renin-stimulating/aldosterone-suppressing test for PA detection.
Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. t-kita@po.sphere.ne.jp
Toshihiro
T
Kita
Mariko
M
Tokashiki
Kazuo
K
Kitamura
D053607:Adrenomedullin / Q000627:therapeutic use*; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D053607:Adrenomedullin