Effect of renal perfusion pressure on renal function, renin release and renin and angiotensinogen gene expression in rats

1. A study was undertaken to examine the influence of acute renal perfusion pressure (RPP) reduction on renin release, renal renin and angiotensinogen gene expression and the role played by angiotensin II in these responses. 2. In chloralose-urethane anaesthetised rats, reduction of RPP to 60 mmHg f or 3 h in vehicle or losartan-treated (5 days at 10 mg: kg(-1) bis in die ( b.i.d.)) rats decreased renal blood flow by 46 and 29 % (both P < 0.001), r espectively, glomerular filtration rate by 45 and 57 % (both P < 0.001), re spectively, and sodium excretion by 96 and 98% (both P < 0.01). 3. Chloralose-urethane anaesthesia and surgery caused a rise in plasma reni n activity but was associated with a suppression of renal renin (50%, P < 0 .01) and angiotensinogen (40%, P < 0.05) gene expression. Following reducti on of RPP to 60 mmHg for 3 h, plasma renin activity was increased more than 7-fold (P < 0.001) and renal renin gene expression about 2-fold (P < 0.05) . 4. Chronic (5 days) blockade of angiotensin II receptors with losartan elev ated plasma renin activity some 29-fold (P < 0.001) and caused a marked inc rease (30-fold, P < 0.05) in renal renin gene expression, compatible with a ngiotensin II exerting a negative feedback control on renin release and gen e expression. Reduction of RPP to 60 mmHg for 3 h in these animals had litt le effect on renal renin gene expression. 5. From these findings it can be concluded that (a) chloralose-urethane ana esthesia and surgery had a stimulatory effect on renin release but suppress ed basal levels of renal renin and angiotensinogen gene expression; (b) acu te reduction of RPP for 3 h could stimulate renin gene expression in the re nin producing cells; and (c) the negative feedback control of angiotensin I I on renin release and synthesis which was evident following chronic losart an treatment was not apparent during short-term reduction of RPP.