ABSTRACT
INTRODUCTION Renin catalyses the fust, rate-limiting tep in the renin-angioten in ca cade that control va cular tone, fluid volume and sodium excretion by indirectly regulating the production of angiotensin II (Scheme 1). The octapeptide, angioten in II (Ang II), and angioten in III derived from it are hjghly potent va ocon trictor that orche trate a chain of event leading to elevated blood pres ure. While angioten in-converting enzyme (ACE), which cataly e the second tep, ha a broad pectrum of sub trate , angioten inogen i the only major phy iologic substrate for renin. Because of thi exqui ite pecificity, inhibition of renin is widely expected to provide elective therapy for hyperten ion, conge tive heart fajJure and a sociated degenerative disorders linked to Ang H. Hence, the three-dimensional structures of renin-inhibitor complexe have long been ought a an aid to the discovery of clinically effective antihypertensive agents (Uim and Greenlee, 1989). It i worth noting in this context that it wa the ob ervation a century ago that hyperten ion could be induced in dogs by injection of kidney extract (Tiger tedt and Bergman, 1898) that eventually led to the characterization of the renin-angioten in y tern (RAS).
