Kallikrein-kinin (KKS) and Renin-angiotensin-aldosterone System (RAAS) in Primary Aldosteronism

Hyperaldosteronism Clinical Trial

Status Completed

Clinical Trial Summary

The tissue kallikrein-kinin (KKS) and renin-angiotension-aldosterone system (RAAS) had been implicated in regulating blood pressure and electrolyte homeostasis. Both of the KKS and RAAS may work coordinately to regulate salt metabolism, local blood flow. Thus, we conducted this study to elucidate, first, whether some alterations in components of the kallikrein-kinin system could do effect on aldosterone secretion.

Previous study has shown the post captopril plasma aldosterone concentration (PAC)/ plasma rennin activity (PRA) ration (ARR) was a reliable method for diagnosis of primary aldosteronism (PA). The ARR change by angiotensin II receptor blockade was reported to be significantly higher than that by ACE inhibitor. This study assessed whether angiotensin II receptor blockade offers any additional advantage in the diagnosis of PA. Clinically we evaluated the sensitivity and specificity of captopril (angiotensin-converting enzyme inhibition) and losartan (angiotensin II type 1 receptor blocker) test in PA patient. This interaction mechanism, in term, could further explain the interaction of KKS and RAAS.

Clinical Trial Description

Hypertension affects 20% to 25% of adult population. Most patients are diagnosed as having essential or primary hypertension. Up to 10% to 15 % have an identifiable cause and many of those have an adrenal basis [Miroslava H. et al., 2002]. The tissue kallikrein-kinin (KKS) and renin-angiotension-aldosterone system (RAAS) had been implicated in regulating blood pressure and electrolyte homeostasis. Recent studies in humans indicate that the vasodilator tissue KKS, the counterpart of the tissue RAAS, is also expressed in the adrenal gland. The adrenal gland regulates sodium and water excretion and reabsorption through the release of aldosterone and corticosterone. Previous study reveals an anatomical linkage between the tissue KKS and sodium and water metabolism. Both of the KKS and RAAS may work coordinately to regulate salt metabolism, local blood flow. In contrast, although many investigators have supported the notion that Ang II and BK physiologically antagonize each other's effects on blood pressure, there are many instances where the two peptides exert common actions. For example, the Bradykinin also stimulates aldosterone release from adrenocortical cells through B2 receptors. Furthermore, the AT1 receptor and the bradykinin (B2) receptor form stable heterodimers, the two major signaling proteins triggered by AT1. In vitro studies (Margolius 1995) have shown that kallikrein acts as a prorenin-activating enzyme, and that tissue kallikrein can generate angiotensin II.

However, the interactions between both systems are complex and not always simply antagonistic. The interactions of the two systems on aldosterone secretion are not examined Thus, we conducted this study to elucidate, first, whether some alterations in components of the kallikrein-kinin system could do effect on aldosterone secretion.

Our study provides evidence that bradykinin contributes substantially to the aldosterone secretion with or without the effects of angiotensin. The data also could confirm whether ATR2-Bradykinin-B2-aldosterone really works. We want to realize the expression of angiotensin and bradykinin in the adrenal gland and hypertension related to these systems.

Previous study has showed the post captopril plasma aldosterone concentration (PAC)/ plasma rennin activity (PRA) ration (ARR) was a reliable method for diagnosis of primary aldosteronism (PA). The ARR change by angiotensin II receptor blockade was reported to be significantly higher than that by ACE inhibitor. This study assessed whether angiotensin II receptor blockade offers any additional advantage in the diagnosis of PA. Clinically we evaluated the sensitivity and specificity of captopril (angiotensin-converting enzyme inhibition) and losartan (angiotensin II type 1 receptor blocker) test in PA patient. This interaction mechanism, in term, could further explain the interaction of KKS and RAAS. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Hyperaldosteronism

• NCT number: NCT00155064
• Study type: Interventional
• Source: National Taiwan University Hospital
• Status: Completed
• Phase: Phase 4
• Start date: July 2002
• Completion date: December 2005