Molecular biology and pathophysiology of the intrarenal renin-angiotensin system

There has been considerable interest in the existence of an intrarenal renin-angiotensin system and its physiological implications. Recent demonstrations of renin, angiotensinogen and angiotensin converting enzyme messenger (m)RNAs in the kidney have provided strong evidence for the presence of an independent local system. This has been further supported by the demonstration of tissue-specific regulation of renin and angiotensinogen mRNA expression which may lead to differential systemic and intrarenal angiotensin activities. Using in situ hybridization, we have localized the intrarenal sites of gene expression and possible angiotensin production. One major site appears to be the proximal tubule, where local angiotensin can regulate sodium reabsorption and urine pH. Renin and angiotensinogen mRNA expressions are regulated by several common factors. In particular, sodium depletion stimulates the expression of both genes in the kidney, increasing the production of intrarenal angiotensin that is important in maintaining sodium homeostasis. Renal renin and angiotensinogen mRNA levels are altered in experimental heart failure and the spontaneously hypertensive rat (SHR). These changes in intrarenal renin and angiotensinogen mRNA expression may be important in the renal pathophysiology of these diseases.