Changes in the renin-angiotensin system after nephrectomy and adrenalectomy.
The study investigates the change in angiotensinogen (Aogen), angiotensin I (AngI) and renin plasma concentration after nephrectomy and adrenalectomy. The aim of the study was to elucidate the mechanisms that are involved in the up regulation of the Aogen plasma levels after nephrectomy and the contribution of the adrenals. Rats were treated with the beta 1-selective adrenoceptor blocker, atenolol, and with the angiotensin antagonist, DuP 753 in order to inhibit renal renin release and to check whether the increase in plasma Aogen after nephrectomy is mediated by angiotensin (AngII), respectively. The plasma Aogen levels increase approx. 5-fold 24 h after nephrectomy. This increase is significantly reduced in the presence of atenolol. After nephrectomy plus adrenalectomy there is a maximal increase of 60% in plasma Aogen levels 8 h after surgery and a subsequent decline. In the presence of atenolol this increase is even smaller. In contrast after adrenalectomy the plasma Aogen levels continuously declined. In the presence of atenolol the plasma Aogen levels were approx. 20% higher at time 0 but declined with the same slope as after adrenalectomy without atenolol treatment. Treatment with DuP 753 caused an almost complete inhibition of the increase in Aogen plasma levels after nephrectomy. Significantly higher Aogen levels were found only after 24 h. At time 0, immediately after nephrectomy the plasma AngI levels were increased compared to the respective control rats. Significantly higher AngI values (P < 0.05) could also be observed in nephrectomized rats and in nephrectomized plus adrenalectomized rats at time 0 in the presence and absence of atenolol and DuP 753, respectively. In contrast after adrenalectomy alone the AngI levels at time 0, were not different from those of the controls. Subsequently the AngI levels increased at a similar rate as after adrenalectomy in the presence of atenolol. These findings suggest that the increase in plasma Aogen after nephrectomy is essentially mediated by AngII via an adrenal mechanism. It seems likely that this process is triggered by renin released during surgery. The increased renin release after adrenalectomy that is responsible for the increased degradation of Aogen seems not to be mediated by a sympathetic stimulation of the renal beta 1-adrenoceptors.
Hilgenfeldt
U
U
Department of Pharmacology, University of Heidelberg, Germany.
Schwind
S
S
D000315:Adrenalectomy; D000803:Angiotensin I / Q000097:blood; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System
D000808:Angiotensinogen; D000803:Angiotensin I; D012083:Renin