Effects of Long-Term Enalapril and Losartan Therapy of Hypertension on Cardiovascular Aldosterone

Abstract

Background: Plasma aldosterone escape is found during long-term angiotensin-converting enzyme inhibitor therapy. Evidence for aldosterone production in cardiovascular tissues raised the question of whether or not aldosterone escape occurs in these tissues. Method: Spontaneously hypertensive rats were treated with enalapril (20 mg/kg/day) and losartan (50 mg/kg/day) for 20 weeks; untreated spontaneously hypertensive and Wistar rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high-performance liquid chromatography, and radioimmunoassay for aldosterone were performed. Results: The results showed that enalapril failed to significantly inhibit aldosterone production in mesenteric artery, myocardium and plasma. Losartan significantly inhibited aldosterone production to that of Wistar rats in the mesenteric artery, myocardium and plasma. Conclusion: This study provides the first evidence that long-term angiotensin-converting enzyme inhibition therapy induces aldosterone escape in hypertensive cardiovascular tissues, and angiotensin II subtype 1 receptor antagonist does not induce aldosterone escape in mesenteric artery, myocardium and plasma of spontaneously hypertensive rats.

Aldosterone and TGF-β1synergistically increase PAI-1 and decrease matrix degradation in rat renal mesangial and fibroblast cells

“…Elevated plasma aldosterone levels are usually observed in patients chronically treated with ACEi by a phenomenon known as "aldosterone escape" (48). The elevated aldosterone level is seen not only in plasma but also in tissue due to alternative pathways of Ang II generation including chymase and chathepsin G (34). Although it was once thought that aldosterone acts primarily as a circulating hormone involved in the regulation of sodium excretion through mineralocorticoid receptor (MR)-dependent mechanisms, evidence has been mounting to suggest that aldosterone also contributes to inflammatory and fibrotic effects that were previously attributed solely to Ang II (16,53).…”

RAAS escape: A real clinical entity that may be important in the progression of cardiovascular and renal disease

“…However, the escape effects do not seem to be limited to patients with CHF or left ventricular hypertrophy, because despite the fact that ACE inhibitors reduce the severity of proteinuria in patients with nondiabetic renal disease, a proportion of these patients escape the antiproteinuric effect and subsequently develop an exacerbation of renal dysfunction [74]. Adding an ARB to an ACE inhibitor decreases the magnitude of "aldosterone synthesis escape" in animal models [75,76] but does not explain all the effects observed in the escape groups in human trials [77][78][79].…”