TISSUE RENIN-ANGIOTENSIN SYSTEM:A Site of Drug Action?

Abstract

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.

Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

“…This gives rise to the possibility that drugs acting on tissue RAS might ameliorate some of these disorders. In fact, a recent study has suggested functional consequences of the action of drugs on tissue RAS (Zimmerman & Dunham 1997).…”

Targeting of Captopril to the Kidney Reduces Renal Angiotensin-Converting Enzyme Activity without Affecting Systemic Blood Pressure

“…Furthermore, ACE inhibitors reduce urinary protein excretion in renal disease and exert a longterm renoprotective effect (Ritz et al, 2000;Taal and Brenner, 2000), despite the incomplete antiproteinuric effect that only reaches an average of approximately 50% (Lees et al, 1990). Both systemic and local ACE inhibition are likely to contribute to the beneficial effect of ACE inhibitors, although their relative contributions remain an object of study (Anderson, 1997;Zimmerman and Dunham, 1997;Fogo, 2001). Drug targeting of an ACE inhibitor to the kidney can be an interesting approach to gain insight into the role of the local ACE in renal (patho)physiology.…”

Effects of Maternal Renal Dysfunction on Fetal Development

“…Exposure to maternal low protein diet in utero induces IUGR and increases expression of glomerular AT1 receptors and reduces AT2 receptor expression in young rat (Battista et al, 2002;Sahajpal & Ashton, 2005). A low protein diet of the mother is associated with lower birth weight and higher blood pressure in offspring, due to the suppression of renin mRNA and the decrease in the angiotensin II levels in the newborn rat kidney (Woods et al, 2001;Zimmerman & Dunham, 1997).…”