Circulating versus local renin-angiotensin system in cardiovascular homeostasis.

The renin-angiotensin system has traditionally been viewed as an endocrine system. Recent data demonstrate that renin and angiotensinogen genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesize angiotensin has changed our understanding of the physiology of the renin-angiotensin system. These potential autocrine-paracrine systems may be important in the regulation of local tissue functions in addition to the circulating endocrine system. The activity of the tissue system under different conditions can influence the pharmacologic response to inhibitors of the renin-angiotensin system. For example, evidence suggests that tissue angiotensin-converting enzyme (ACE) may be the primary site of action of ACE inhibitors. Consequently, the duration of action of an ACE inhibitor may be more dependent on the duration of tissue ACE inhibition than on the drug's serum half-life. The differential effects of these pharmacologic inhibitors on the tissue renin-angiotensin systems may form the basis of differentiation between the various ACE inhibitors.