Serum Potassium, Thiazides, Aldosterone, and Mineralocorticoid Receptors

Abstract

Alderman et al 1 on the clinical significance of hypokalemia and hyperkalemia in the antihypertensive treatment and prevention of cardiovascular complications. The conclusion was that, in most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazides. Chlorthalidone reduces the risk of congestive heart failure, in comparison with lisinopril and amlodipine, 1 but it also activates the renin-angiotensinaldosterone system. We address the issue that, beyond plasma potassium levels, during thiazides, the activation of the renin-angiotensinaldosterone system and, in particular, the stimulation of mineralocorticoid receptors (MRs) are key determinants in the inflammatory process and the progression of cardiovascular disease.The Randomized Aldactone Evaluation Study and Eplerenone Post-AMI Heart Failure Efficacy and Survival Study 2 have shown that low doses of spironolactone (SP) or eplerenone, added to the standard therapy including thiazides for treatment of severe heart failure, improve survival by 30%. An interesting demonstration that the positive effect of SP is not attributed to amelioration of serum potassium but to the blocking of MRs comes from the study by Ma et al. 3 These authors showed that, in hypertensive patients, SP could reduce plasminogen activator inhibitor 1 concentration in serum, whereas triamterene was ineffective; hydrochlorothiazide indeed worsened plasminogen activator inhibitor 1 concentration, which is a known marker of inflammation. The conclusion was that the principal effect of SP in the reduction of cardiovascular risk is the blocking of MR and not the increase of potassium. We also found that canrenone is able to protect MRs from the inflammatory action of aldosterone in mononuclear leukocytes in vitro, whereas amiloride is not. 4 From all of these considerations, it can be concluded that thiazides can reduce blood pressure and ameliorate congestive heart failure but can only partially protect from cardiovascular risk because of an increase of aldosterone, leading to inflammatory reaction at the level of the kidney, heart, and lymphocytes, independent from the sodium intake. SP or its derivatives improve serum potassium, reduce insulin resistance, and prevent the inflammatory effect of aldosterone. SP activates all of the components of the renin-angiotensin-aldosterone system, but MRs are blocked, neutralizing the proinflammatory effect of aldosterone. These discrepancies point out the fundamental role of MR even in situations of volume depletion and activation of the renin-angiotensin-aldosterone system. 5 Previous studies have ascribed to angiotensin II a key role in the onset and progression of cardiovascular damage, but it is more likely that the increase of aldosterone and MR-mediated effect is the principal factor involved in the inflammatory reaction at the level of the target tissues.From all of these considerations it follows that the treatment of hypertension with MR an...

Licorice: From Pseudohyperaldosteronism to Therapeutic Uses

“…The authors reported a significant reduction of the prevalence of heart failure relapse and cardio-cerebrovascular accidents when the MR blockers were added to the conventional treatments of these pathological conditions (18–20). The protective effect of MR blockers is opposite to the effect of other diuretics that increase aldosterone secretion and inflammatory reaction (21, 22). Recent researches are exploring the protective effect of spironolactone as an anti-inflammatory and immunomodulatory agent even in the treatment of other pathological conditions, such as rheumatoid arthritis and central serous chorioretinopathy (23, 24).…”

Considerations for the Assessment of Salt Intake by Urinary Sodium Excretion in Hypertensive Patients

“…The only clinical situations associated with an increase in mineralocorticoids and volume expansion are primary aldosteronism and pseudohyperaldosteronism . The inflammatory effect of aldosterone is also evident in patients treated with thiazides and amiloride, while aldosterone receptor blockers are able to prevent cardiovascular risk . Thiazides and furosemide can reduce blood pressure but they increase aldosterone, and mineralocorticoid receptors are not blocked as occurs with spironolactone derivatives.…”

Potential Interaction of Green Tea Extract with Hydrochlorothiazide on Diuretic Activity in Rats

“…Several studies have now demonstrated that a significant incidence of ventricular ectopic activity with diuretic-induced hypokalemia is responsible for sudden death [ 4 ]. Apart from plasma potassium levels associated with thiazides, the activation of the renin-angiotensin-aldosterone system and, in particular, the stimulation of mineralocorticoid receptors are key determinants in the inflammatory process and the progression of cardiovascular disease [ 5 ].…”