Kallikrein-kinin (KKS) and Renin-angiotensin-aldosterone System (RAAS) in Primary Aldosteronism
Condition: Hyperaldosteronism
MeSH terms: Hyperaldosteronism
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): captopril, Losartan (drug)
Intervention type(s): Drug
Intervention MeSH terms: Losartan; Captopril
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Primary aldosteronism; kallikrein; aldosterone; captopril