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Kallikrein-Kinin (KKS) and Renin-Angiotensin-Aldosterone System (RAAS) in Primary Aldosteronism

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2002 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00155064
First received: September 9, 2005
Last updated: December 19, 2005
Last verified: July 2002

September 9, 2005
December 19, 2005
July 2002
Not Provided
Diagnosis of primary aldosteronism
Same as current
Complete list of historical versions of study NCT00155064 on ClinicalTrials.gov Archive Site
Subgroup analysis of primary aldosteronism
Same as current
Not Provided
Not Provided
 
Kallikrein-Kinin (KKS) and Renin-Angiotensin-Aldosterone System (RAAS) in Primary Aldosteronism
Not Provided

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Hyperaldosteronism
Drug: captopril, Losartan (drug)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
July 2007
Not Provided

Inclusion Criteria:

Patients with hypertension admitted for the diagnosis of primary aldosteronism

Exclusion Criteria:

Pregnant or lactating women. (Pre-menopause women, capable of bearing children will undergo pregnancy test), hypertension without discontinuous b-blocker, ACEI or ARB for more than 10 days.

Both
18 Years to 80 Years
No
Contact: Kwan-Dun Wu, MD, PhD +886-2-23562082 kdw@ha.mc.ntu.edu.tw
Taiwan
 
NCT00155064
9361700632
Not Provided
Not Provided
National Taiwan University Hospital
Not Provided
Study Chair: Kwan-Dun Wu, Md, PhD National Taiwan University Hospital
Study Director: Vin-Cent Wu, MD National Taiwan University Hospital
National Taiwan University Hospital
July 2002

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP