Hypothesis: ACE2 Modulates Blood Pressure in the Mammalian Organism Academic Article uri icon

abstract

  • The renin-angiotensin system (RAS) is currently considered a central regulator of blood pressure in the mammalian organism. Even though renin was first described in 1898, it was only in the late 1970s and early 1980s that the important contribution of the RAS to mammalian physiology began to be truly recognized. Any doubts that may have arisen as to its relative importance and contribution to cardiovascular disease in general, and to hypertension in particular, were totally dissipated with the advent of angiotensin-converting enzyme (ACE) inhibition for clinical and therapeutic use. It is now well established that hyperactivation of the RAS invariably 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. With the recently discovered angiotensin-converting enzyme 2 (ACE2),1–3 it appears that a new unexpected direction is unfolding in the RAS paradigm which will change altogether our perception of how this important system works. Our knowledge of RAS has led us until recently to focus primarily on one major axis of the system that is initiated by angiotensinogen, and that is followed by generation of angiotensin I (Ang I) through the catalytic action of renin, hydrolysis and removal of 2 amino acids, primarily by the action of the dipeptidase ACE to yield angiotensin II (Ang II), and occupation of the angiotensin receptors. Ang II is, among its other known biological effects, a most potent vasoconstrictor which can induce hypertension. In this axis, ACE has been looked on as a central modulator of the system and consequently has been targeted with a high degree of success by the pharmaceutical industry. Recent data lead us to realize that this axis represents only 1 of 2 arms of the renin-angiotensin system. The second arm is also …

publication date

  • January 1, 2003