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

Abstract

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 for 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), respectively, glomerular filtration rate by 45 and 57 % (both P < 0.001), respectively, and sodium excretion by 96 and 98 % (both P < 0.01). 3. Chloralose-urethane anaesthesia and surgery caused a rise in plasma renin activity but was associated with a suppression of renal renin (50 %, P < 0.01) and angiotensinogen (40 %, P < 0.05) gene expression. Following reduction 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 elevated plasma renin activity some 29-fold (P < 0.001) and caused a marked increase (30-fold, P < 0.05) in renal renin gene expression, compatible with angiotensin II exerting a negative feedback control on renin release and gene expression. Reduction of RPP to 60 mmHg for 3 h in these animals had little effect on renal renin gene expression. 5. From these findings it can be concluded that (a) chloralose-urethane anaesthesia and surgery had a stimulatory effect on renin release but suppressed basal levels of renal renin and angiotensinogen gene expression; (b) acute reduction of RPP for 3 h could stimulate renin gene expression in the renin producing cells; and (c) the negative feedback control of angiotensin II on renin release and synthesis which was evident following chronic losartan treatment was not apparent during short-term reduction of RPP.

Figure 1. Changes in plasma renin activity after sham operation, 3 h reduction of RPP, losartan injection or 3 h reduction of RPP in losartan-treated rats

Effect of renal perfusion pressure reduction to 60 mmHg for 3 h in losartan-treated, 10 mg kg⁻¹ b.i.d. for 5 days i.p., (Los-60 mmHg) or non-treated (60 mmHg) rats on plasma renin activity (PRA). In the Sham group, rats had undergone 3 h of sham stimulation. Control non-treated (Cnt) and losartan-treated (Los-Cnt) rats were immediately killed.

Figure 2. Northern blot autoradiographs for renin (top), angiotensinogen (AGT; middle), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH; bottom) mRNAs

Comparisons were made between left kidneys taken from rats either losartan treated, 10 mg kg⁻¹ b.i.d. for 5 days i.p., (Los-Cnt) or non-treated (Cnt) which were immediately killed, and losartan-treated rats in which RPP was reduced to 60 mmHg for 3 h (Los-60 mmHg).

Figure 3. Changes in renal renin gene expression after 3 h reduction of RPP or sham operation, losartan injection or 3 h reduction of RPP in losartan-treated rats

Comparisons were made between left kidneys taken from groups of rats which were immediately killed (Cnt) and in which RPP was reduced for 3 h to 60 mmHg (60 mmHg), or remained unchanged (Sham) (A), and left kidneys taken from losartan-treated rats, 10 mg kg⁻¹ b.i.d. for 5 days i.p. (Los-Cnt), and losartan-treated rats in which RPP was reduced to 60 mmHg for 3 h (Los-60 mmHg) (B). The ratio of left renal renin per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA densitometric readings (renin/GAPDH mRNA) was expressed relative to the mean of those of the control group (Cnt) and was given as a percentage of Cnt.

Figure 4. Changes in renal angiotensinogen gene expression after 3 h reduction of RPP or sham operation, losartan injection or 3 h reduction of RPP in losartan-treated rats

Comparisons were made between left kidneys taken from groups of rats which were immediately killed (Cnt) and in which RPP was reduced for 3 h to 60 mmHg (60 mmHg), or remained unchanged (Sham), losartan-treated rats, 10 mg kg⁻¹ b.i.d. for 5 days i.p., (Los-Cnt) and losartan-treated rats in which RPP was reduced to 60 mmHg for 3 h (Los-60 mmHg). The ratio of left renal angiotensinogen (AGT) per glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA densitometric readings (AGT/GAPDH mRNA) was expressed relative to the mean of those of the control group (Cnt) and is given as a percentage of Cnt.