Discovery of the angiotensin converting enzyme (ACE) in the pulmonary circulation. Search for its inhibitor led to the synthesis of ACE inhibitors which are now used for the treatment of hypertension, congestive hear failure and diabetic kidney disorder.

1. DISCOVERY OF ANGIOTENSIN CONVERTING
ENZYME IN THE LUNG
Kevin KF Ng, MD, PhD, FRACP
Former Associate Professor of Pharmacology
University of Singapore
Former Associate Professor of Medicine
University of Miami, Florida
Presented at Department of Medicine, Tan Tock Seng Hospital, Republic of Singapore: Jan 22, 2016

2. Discovery of the lung angiotensin converting enzyme 1967
 History of the renin-angiotensin system.
 Vane’s blood bathed organ superfusion technique.
 Estimation of half-lives in circulating blood.
 Disappearance of angiotensin II in vascular beds.
 Estimation of conversion of angiotensin I to angiotensin II in circulating blood.
 Disappearance of angiotensin I in vascular beds
 Evidence that angiotensin I is converted to angiotensin II in the lungs.
 The lung as an endocrine organ.
 Subsequent research on endothelium of capillaries of the pulmonary vascular bed.
 Recent advances in basic science and clinical research.

3. Timeline on Discovery of Pulmonary
Angiotensin Converting Enzyme 1890-1967

4. Assay of Hormones in Blood

5. Isolated Bioassay Organs

6. Reactions of isolated organs to physiological concentrations of
substances (1-5 ng/ml) likely to be found in blood

7. The dynamics of the renin-angiotensin system 1966

8. Vane’s blood-bathed organ technique: superfusion & incubation circuit

9. Half-life of angiotensin II in circulating blood (sec)

10. Disappearance of a substance in one circulation through vascular bed

11. Disappearance of angiotensin II in vascular beds

13. % conversion of angiotensin I to angiotensin II in circulating blood

14. % conversion of angiotensin I to angiotensin II in blood and vascular beds
5 sec90 sec

15. Disappearance of Angiotensin I and Angiotensin II in vascular beds

16. Evidence that angiotensin I is converted to angiotensin II in lungs
1. Intravenous angiotensin I.
2. IV Exogenous Renin infusion.
3. Endogenous Renin release
from Golblatt kidney.
4. Lung perfusate from isoalated
lungs.

17. A New Concept of Renin-angiotensin System in 1967

19. The endothelium and ectoprotein angiotensin converting enzyme

20. Vasoactive substances metabolized by the endothelium
http://ceaccp.oxfordjournals.org/content/early/2013/01/10/bjaceaccp.mks060.full.pdf+html

21. Vasoactive substances synthesized by the endothelium of lungs

22. Pulmonary extraction, metabolism or both of drugs used in anesthesia

23. Respiratory and Non-respiratory functions of the lung
 Respiratory function: Gas exchange of Carbon Dioxide for Oxygen
 Non-respiratory functions: Activation, Inactivation, Free passage of vasoactive substances
 Paracrine functions : Nitric oxide (NO), Prostacylcin (PGI), Platlete acting factor, Endothelin.

24. Impact of the discovery of Lung Angiotensin Converting Enzyme (ACE)
since 1967.
 Unique function of the pulmonary angiotensin converting enzyme (ACE) in converting the
inactive angiotensin I to the active angiotensin II.
 Selective filter of vasoactive substances in the circulation.
 The endocrine function of the lung in the release of active pharmacological substances.
 Development of angiotensin converting enzyme inhibitor (ACE inhibitor) in the treatment of
hypertension, congestive heart failure and diabetic kidney disease since 1981.
 Recognition of the role of plasma ACE in pathological states e.g. sarcoidosis.
 Recent research in ACE-2.

25. Number of counts on PubMed related to ACE, ACEI, ARB since 1967

27. References
 KKF Ng: “The dynamics of the renin-angiotensin system”.
Ph. D. Thesis, University of London, 1968.
 RL Hodge, KKF Ng and JR Vane: Disappearance of angiotensin from the circulation of the dog.
Nature (1967),215,138-141.
 KKF Ng and JR Vane: Conversion of angiotensin to angiotensin II.
Nature (1967), 216,762-766.
 KKF Ng and Vane: Fate of angiotensin I in the circulation.
Nature (1968), 218,144-150.
 KKF Ng and Vane: Some properties of angiotensin converting enzyme in the lung.
Nature (1970) 225, 1142-1144