MINERALOCORTICOIDS, SALT, HYPERTENSION - EFFECTS ON THE HEART

In uninephrectomized rats on 1% NaCl solution to drink, aldosterone (0 .75 mu g/h subcutaneously for 8 weeks) raises blood pressure and cause s marked interstitial and perivascular cardiac fibrosis, effects not s een in animals on a low salt intake. In extending these initial findin gs, we have shown that cardiac fibrosis (i) is not reversed by correct ion of mineralocorticoid-induced hypokalemia; (ii) appears not to invo lve the plasma or tissue renin-angiotensin systems, as fibrosis is lar gely unaffected by concurrent administration of Losartan or Perindopri l; (iii) is independent of cardiac hypertrophy, in that it is equally seen in right and left ventricles, and in rats rendered hypertensive w ithout cardiac hypertrophy by the administration of 9 alpha-fluorocort isol; (iv) is independent of elevated blood pressure, in that it is fo und in normotensive animals infused peripherally with aldosterone and intracerebroventricularly with the mineralocorticoid receptor (MR) ant agonist RU28318; (v) is via classical MR, in that it is blocked by con current administration of the MR antagonist potassium canrenoate; and (vi) may or may not be a direct cardiac effect, inasmuch as data for i n vivo effects on collagen formation by cardiac fibroblasts are confli cting. Although there is a high probability that the action of aldoste rone to cause cardiac fibrosis in this experimental model is an effect via non-epithelial MR, the locus of aldosterone and collagen depositi on. In addition, and in particular, the mechanisms underlying the cruc ial contribution of high salt intake in this model of mineralocorticoi d excess await exploration.