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Plasma levels of adrenomedullin (AM), a bioactive peptide produced in adipose tissue, have been shown to be higher in obese patients than in non-obese patients, but little is known about gender differences in plasma AM levels. The aims of this study were to clarify gender-related alterations in plasma AM levels and to examine the body weight (BW) gain–plasma AM relationship in the general population. We measured plasma AM levels of 346 local residents (62.0±8.9 years, mean±s.d.) in the Kiyotake area, Japan, who underwent a regular health check-up, by a specific fluorescence immunoassay. Plasma AM levels in the female residents were lower than that in the males, and multiple regression analysis revealed a possible gender difference in plasma AM. The AM levels were significantly correlated with BMI or waist circumference in women, but such a relationship was not seen in men. When the subjects were divided into two groups by results of a questionnaire about BW gain of 10 kg or more since the age of 20 years, the plasma AM level of women with BW gain ≧10 kg was significantly higher than that in those without BW gain, although no difference was noted between the men with and without BW gain. In conclusion, possible gender differences were noted in the plasma AM levels and in the BW gain–plasma AM relationship in the general population. The plasma AM levels in the female residents without BW gain seem partly attributable to the lower AM of women.

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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 À1 min À1 ) for 27 h, followed by a 15-h recovery period, in a control group (essential hypertensives with plasma aldosterone levels p100 pg ml À1 , n¼7) and in a PA group (n¼5). 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 À1 , Po0.01). In the control group, aldosterone release suppression was significant but limited (81.7 ± 9.1 to 47.9 ± 9.9 pg ml À1 , Po0.01). 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 Keywords: adrenomedullin; aldosterone; C-reactive protein; humans; primary aldosteronism INTRODUCTION Adrenomedullin (AM) is a potent hypotensive peptide found ubiquitously in tissues and organs, especially in cardiovascular tissues, the kidneys, lungs and endocrine glands. AM has multiple functions in a wide range of tissues and acts mainly as a vasodilatory and proliferation-inhibitory factor. 1 AM was initially identified in the adrenal medulla, but similar densities of AM were detected in the zona glomerulosa of the adrenal cortex, where AM suppresses aldosterone release. 2,3 In addition, expression of AM and its receptor was detected in Conn's adenoma cells, and AM exerted aldosterone antisecretagogue action and proliferative effects on cultured Conn's adenoma cells. 4 These findings suggest that endogenous AM may be an important modulator of aldosterone release in normal and pathogenic hyperaldosteronism. In addition, AM antagonized aldosterone-induced vascular or cardiac remodeling 5,6 and suppressed aldosterone-induced oxidative stress in a malignant hypertensive model. 7 The characteristics that define this compound, from its release to alterations in target organs, suggest that AM may be an endogenous anti-aldosterone factor, especially in the cardiovascular system.