Students

Name: Frank Ding Bao-Guo

Post: Full-time Ph.D

Origin: Mainland China, Beijing 301 Hospital

Enrolled: 1997 - 2001

Title of Thesis:

Interaction between the rennin-angiotensin system and its implication in the pathogenesis of post-infarction heart remodeling

Outline of the Thesis:

Background: The blockade of renin-angiotensin-aldosterone system (RAAS) has recently become the mainstay in the management of heart failure (CHF). However, the effects of RAAS blockade on sympathoadrenal system in the pathogenesis of CHF are currently not well understood.

Objectives: To examine the effects of candesartan (an AT1 receptor antagonist) and ramipril (a ACE inhibitor) on sympathoadrenal activity as well as postinfarction heart remodelling in rats, and to examine the acute effect of candesartan and ramipril on electrically induced adrenal catecholamine (CA) release in dogs.

Methods: Rats undergoing coronary artery ligation were given RAAS blocking agents from the 2nd week after the surgical procedure till the end of the study (12 weeks). Daily urinary CA excretion was measured regularly as an indicator of sympatho-adrenal activity. The acute effects of candesartan and ramipril on the electrically induced adrenal CA release were investigated in anaesthetised dogs.

Results: The daily urinary noradrenaline (NA) and dopamine (DA) excretion peaked at the 1st week and 8th week respectively after coronary ligation and remained higher than sham-operated at the 12th week (P<0.05). The levels were noted to decrease to baseline values at the 4th week as seen in the sham-operated rats. The daily urinary NA and DA in rats on candesartan (2mg/kg) and mixture of candesartan (2mg/kg) and ramipril (2mg/kg) remained significantly higher than those of sham-operated rats throughout the study (P<0.05). Candesartan and ramipril used alone or in combination significantly improved the indices of haemodynamics and morphology compared with untreated postinfarction rats (P<0.05).

In anaesthetised dogs, candesartan (0.8mg/kg) and ramipril (0.125mg/kg), administered alone or in combination, significantly inhibited the adrenal CA release in response to electrical stimulation. However, the high-dose candesartan showed significantly less inhibitory effect than low-dose.

Conclusions: Candesartan and ramipril significantly modulated the urinary NA and DA excretion in the early period of after use in postinfarction rats and both drugs significantly improved the results of ventricular remodeling. Candesartan and ramipril significantly inhibited the electrically induced adrenal CA release.

Publications arising from his thesis:

(A) Scientific Papers:

1. Critchley LAH, Ding BG, Fok BSP, Wang DQ, Tomlinson B, James AE, Thomas GN, Critchley JA. The effects of Candesartan and Ramipril on adrenal catecholamine release in anaesthetized dogs. European Journal of Pharmacology 2004; 489: 67-75.
   

(B) Conference Abstracts:

2. 2001. 3^rd HK Diabetes & Cardiovascular Risk Factors, East meets West Symposium. Ding BG, Critchley LAH, Thomas GN, Fok B, Wang DQ, Zhang Y, Tan P, James AE, Tse J, Thomlison B, Critchley JAJH. Acute effect of Candesartan and Ramipril on adrenal catecholamine release.
   
   
3. 2001. 3^rd HK Diabetes & Cardiovascular Risk Factors, East meets West Symposium. Ding BG, Critchley LAH, Thomlison B, Thomas GN, Fok B, Wang DQ, James AE, Critchley JAJH. Chronic efeects of Candersartin and Ramipril on urinary catecholamine excretion in experimental myocardial infarcted rats.
   
   
4. 2001. 9^th ASC HKCC, Hong Kong. Journal of the Hong Kong College of Cardiology 2001; 9: 109. Ding BG, Thomas GN, Critchley LAH et al. Effects of Candesartin and Doxazosin on the sympathoadrenal axis in experimental post-infarction heart failure.