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The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Furthermore, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.The renin-angiotensin system consists of three major components: angiotensinogen, renin (EC 3.4.23.15), and angiotensin-converting enzyme (dipeptidyl carboxypeptidase I, peptidyl-dipeptide hydrolase, EC 3.4.15.1) (1, 2). Angiotensinogen is mainly synthesized in the liver and is secreted into the circulating blood. This peptide precursor is cleaved by the enzyme renin, which is expressed and secreted into the circulation from the juxtaglomerular cells of the kidney. The angiotensin I thus formed is subsequently converted to angiotensin II by angiotensin-converting enzyme. Angiotensin II acts as a potent vasoconstrictor and stimulates release ofaldosterone from the adrenal cortex. The renin-angiotensin system thus plays an important role in the control of blood pressure and hydromineral balance. In our previous studies (3-7), we elucidated the structures, gene organization and regulation of angiotensinogen and renin with the aid of recombinant DNA techniques. To study how the reninangiotensin system is involved in the regulation of blood pressure and in the development of hypertension, we have generated transgenic mice in this investigation that are capable of expressing exogenous rat renin or angiotensinogen or both under the control of the mouse metallothionein I (MT-I) promoter. We here report the generation of hypertensive transgenic mice by introducing the renin and angiotensinogen genes.

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Here we describe the isolation of a rainbow trout cDNA containing an entire GR coding region. Although the encoded protein is highly homologous to other GRs, especially in its DNA binding domain, it contains a nine amino acid insertion between the two zinc fingers. This novel form is found in all rainbow trout tissues examined; however, the testis also contains a splice variant lacking this insert, making it completely continuous to other GRs. In transient transfection assays of cultured cells, the two rainbow trout GR variants activated transcription from the glucocorticoid-responsive mouse mammary tumor virus promoter to comparable levels.

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