New breakthrough in renin angiotensin pathway.

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Dear bloggers, As we all know, the regulation of blood pressure in mammalian organism is primarily concerned with centrally acting Renin Angiotensin System(RAS). It is now very well established that hyperactivation of the RAS leads to hypertension and to a number of other adverse cardiovascular effects that can be, at least in part, prevented by ACE inhibition or angiotensin receptor blockade. But, recent discovery of Angiotensin-Converting Enzyme 2 (ACE2) , has unfold the whole perception that how this system really works.[1-3] The whole break-through of RAS with recent importance of ACE2 is indicated below : Here, Angiotensinogen ------> Ang 1 (1-10) -----> Ang 2 (1-8) -----> Vasoconstriction (Conversion is mediated by ACE) & Recent research explore addition in this pathway, i.e., Ang 1 (1-10) -----> Ang-(1-9) ------> Ang-(1-7) & Ang 2 (1-8) -----> Ang-(1-7) --------------------> Vasodilation (Conversion is mediated by ACE 2) Here, In first arm, the action of the dipeptidase Angiotensin Converting Enzyme (ACE) is the conversion of angiotensin 1(generated by catalytic action of renin from the angiotensinogen) to angiotensin 2, which involves removal of two amino acids from angiotensin 1. Formed angiotensin 2 now act on angiotensin receptor & leads to potent vasoconstriction effect. The second arm of this system is also initiated by angiotensinogen, but is followed by hydrolysis of Ang I to angiotensin 1-9 (Ang-[1-9]) through the catalytic action of the newly discovered monopeptidase ACE2 [1-3] . Ang-(1-9) is hydrolyzed further and looses 2 amino acids by the action of ACE to generate angiotensin 1-7 (Ang-[1-7]), a potent vasodilator peptide that has considerable interest in therapy of hypertension. An additional important action of ACE2 is the hydrolysis of Ang II and removal of one additional amino acid, also producing Ang-(1-7). In fact, the ACE2 catalytic efficiency is 400-fold higher with Ang II as a substrate than with Ang I.[3] Further hypothesis says that, in normal condition there is balance between these two arms, and it will maintain the normotention in mammalian organism. Any imbalance between the 2 arms of the system can result either in hypertension or in hypotension. In conclusion, it can be said that While one considers the RAS, He/She should consider both the arms of RAS with further explosion in therapy of CVS disorders. we can say that studies in different organ systems should be encouraged with respect to the potential involvement of ACE2. Much interest has already been directed at the role of ACE2 with regard to the cardiovascular system with emphasis on the heart.[4,5]. The effect of ACE2 is also studied in renal diseases & finding exert direct effect on renal hemodynamics.[6] REFERENCES : [1] Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275: 33238-33243. [2] Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000; 87: 1-9 [3] Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002; 277: 14838-14843. [4] Bernstein KE. Two ACEs and a heart. Nature. 2002; 417: 799-801. [5] Boehm M, Nabel EG. Angiotensin-converting enzyme 2: a new cardiac regulator. N Engl J Med. 2002; 347: 1795-1797 [6] Ren YR, Garvin JL, Carretero OA. Vasodilator action of angiotensin-(1-7) on isolated rabbit afferent arteriole. Hypertension. 2002; 39: 799-802

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Swagat K. Soni's picture
Author: Swagat K. Soni


Sandhya Sravya malla's picture

very informative and good way of blogging regards PHARMA WARRIORS
Swagat K. Soni's picture

Thanks 4 d same, dear..

Swagat K. Soni Anand Pharmacy college M.Pharm (Pharmacology)

Shreesha Bhat's picture

nice blog....

Shreesha V Bhat Ramanbhai Patel College of Pharmacy, Education campus Changa, Gujarat, India.

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