Increased plasma angiotensinogen in cardiac transplantation patients

Interleukin 6 (IL-6) stimulates the production of angiotensinogen (renin substrate, RS), an acute phase reactant and the precursor of the potent vasoconstrictor angiotensin II. This study assesses the effect of cardiac transplantation on plasma levels of angiotensinogen and interleukin 6.

Effects of cardiac transplantation on plasma levels of renin substrate and IL-6 were studied in twelve patients with NYHA IV end-stage heart failure. Renin substrate, IL-6, plasma renin activity, C-reactive protein and serum amyloid A were determined 1 day before cardiac transplantation, and 1 day, 1 week, 4 weeks and 12 weeks postoperatively. Renin substrate was measured by both direct and indirect radioimmunoassay. An indirect assay measures intact renin substrate only, capable of releasing angiotensin I, while a direct assay measures both intact renin substrate and des-angiotensin I-renin substrate, the residue of renin substrate after cleavage of angiotensin I.

Plasma renin substrate and IL-6 increased significantly on day 1 as compared with preoperative levels. Plasma renin substrate increased (measured by direct and indirect assay) by 64 and 50%, respectively, IL-6 levels by 43%. Plasma IL-6 returned to preoperative (normal) levels by 4-12 weeks. Plasma renin substrate levels remained elevated for the follow-up period of 12 weeks. The direct assay always gave higher values than the indirect assay, presumably due to consumption of renin substrate by renin. Consequently, a negative correlation between plasma renin activity and renin substrate measured with indirect assay was observed.

Our findings suggest that cardiac transplantation brings about an acute phase reaction, mediated partly by IL-6, with increased synthesis of acute phase proteins like renin substrate. This may result in increased angiotensin II levels. Considering the trophic effects of angiotensin II on vascular tissue, increased production of renin substrate may contribute to the development of proliferative cardiovascular changes in heart transplant recipients.