The renin-angiotensin system.

Unravelling of the molecular mechanisms of the action of RAS has been slow. Nature has been rather stingy in revealing bits and pieces of information. Each step of development has depended on the innovation of an appropriate methodology. The uniqueness of the RAS lies in: The function and regulation of the highly specific enzyme renin which specifically catalyses the conversion of the prohormone angiotensinogen to Ang I by an extracellular mechanism. The production of the agonist Ang II takes place in two steps. Ang II and its metabolites exert exceedingly diverse pathophysiological effects, presumably through the complex and multifunctional receptors. The exquisite mechanisms involved in the regulation of renin release and receptor regulation are fascinating. The intricate mechanisms that nature has devised for the checks and balances to maintain steady blood flow and electrolyte balance present a great challenge to biochemists in their attempts to clarify the mechanisms involved at both molecular and cellular levels. In relation to the pathophysiology of hypertension, particularly essential hypertension, there is no question that the RAS plays a pivotal role. Although numerous mechanisms could explain its hypertensinogenic effects, no single mechanism can be identified as the major determinant at the present stage of our knowledge. However, there is an important consensus that the effect of Ang II is manifested slowly at even subpressor doses of Ang II through long-term effects involving remodelling of the cardiovascular and renal system.