Tissue renin-angiotensin system: a site of drug action?

In this review, we present background material that provides partial support for a tissue renin-angiotensin system (RAS). Evidence for the existence of this system relied in part on the use of drugs, which has entailed using low doses or concentrations of angiotensin-converting enzyme inhibitors, renin inhibitors, and angiotensin antagonists to block the RAS in vascular beds and in isolated arteries or organs. Other evidence for a tissue RAS has depended upon measurements of the components of the system, i.e. enzymes, substrates, and mRNAs for these proteins. All of these components were first believed to be present in the heart and blood vessels; however, it is now known that renin in the circulating blood derived from the kidney is used for the local synthesis of angiotensins. The main emphasis of the review is on the renal RAS because it is believed that the local RAS is most prominent in this organ. The renal RAS is probably involved in the long-rather than short-term regulation of renal vascular resistance and maintenance of normal blood pressure through the regulation of sodium reabsorption.