Abstract P011: Source and Catabolism Sites of the Cardio-renal Protective Peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP)

Ac-SDKP is a natural tetrapeptide with anti-fibrotic and anti-inflammatory properties in vascular, myocardial and kidney tissues. It is degraded by angiotensin converting enzyme (ACE) and treatment with ACE inhibitors increases its plasma levels. However the main sites of Ac-SDKP production and catabolism are unknown. Thus, the aim of this study was to determine the source and catabolism sites of Ac-SDKP. Ac-SDKP was measured in brain, thymus, lungs, heart, spleen, kidney, liver, intestine, and bone marrow from male 200-250 gr Sprague Dawley rats. Samples from arterial blood delivered to and venous blood exiting from kidney, spleen, intestine, liver, and lungs were obtained, and the vein to arterial (V-A) plasma levels differences were calculated as an index of organ production or elimination. Additionally, urinary Ac-SDKP excretion over 24 hrs and Ac-SDKP renal clearance were measured. Inulin clearance was also determined. The Stop Flow technique was performed to evaluate the renal handling of Ac-SDKP in different segments of the nephron. The greatest amounts of Ac-SDKP were found in Thymus, Spleen and Bone marrow (111.3±9; 92.2±24; 70.3±17 pmoles/mg of protein respectively), while the lowest values were found in brain, large intestine and heart (10.7±6; 14.8±6 ;19.8±7; pmoles/mg of protein, respectively). Ac-SDKP is secreted by different organs into the circulating blood. The highest V-A difference was found in the spleen (15.2±7 nM), reflecting its production, while the lowest V-A differences was observed in the lungs (-1.2±3.7 nM), reflecting a high degradation of Ac-SDKP in this tissue. No V-A differences were found in kidney (0.98±7 nM). It was not possible to obtain venous samples from Thymus or Bone marrow. The renal clearance of Ac-SDKP was 0.15 ml/min/100g body weight, equivalent to a fractional excretion of 14.5%. The stop flow technique showed the highest Ac-SDKP levels in the distal part of the nephron, while the proximal segments showed the lowest (11 Vs. 4.2 Ac-SDKP/Inulin ratio). In conclusion, Ac-SDKP production occurs mainly in lymphoid organs. Expectedly, high Ac-SDKP degradation was observed in the lungs. In the kidney Ac-SDKP is filtered, probably degraded in the proximal tubule and secreted in the distal tubule.