Aldosterone in salt-sensitive hypertension and metabolic syndrome.
Metabolic syndrome, which is caused by obesity, is now a global pandemic. Metabolic syndrome is an aggregation of hypertension, diabetes and dyslipidaemia. Insulin resistance is a key factor in the development of these components of metabolic syndrome. Concerning the mechanism for the development of hypertension in metabolic syndrome, the lack of insulin resistance in the kidney increases sodium reabsorption by hyperinsulinaemia, leading to sodium retention in the body, and resultant salt-sensitive hypertension. Moreover, hyperaldosteronism, which is caused by adipocyte-derived aldosterone-releasing factors, induces not only salt-sensitive hypertension, but also proteinuria in obese hypertensive rats. Salt loading markedly aggravates proteinuria and induces cardiac diastolic dysfunction in obese hypertensive rats, suggesting that salt and aldosterone exert unfavourable synergistic actions on the cardiovascular system, possibly through the overproduction of oxidative stress. In turn, reactive oxygen species (ROS), which are induced by adipokines such as tumour necrosis factor-alpha, non-esterified fatty acids, angiotensinogen etc., can activate the mineralocorticoid (MR) receptor, in an aldosterone-independent fashion. Therefore, aldosterone/MR activation plays a key role not only in the development of salt-sensitive hypertension, but also in cardiovascular injury in metabolic syndrome, possibly through its function as a feed-forward system.
Fujita
Toshiro
T
Department of Nephrology and Endocrinology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. fujita-dis@h.u-tokyo.ac.jp
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000150:complications*; D024821:Metabolic Syndrome / Q000150:complications*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D000450:Aldosterone