Relaxin mediated renal vasodilation in the rat is associated with falls in glomerular blood pressure

Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory actions which are physiologically important during pregnancy. RLX also has potent antifibrotic actions and is being tested therapeutically in various fibrotic diseases including chronic kidney disease (CKD). Since renal vasodilation may expose the glomerulus to increased blood pressure (P_GC), which exacerbates progression of CKD, we assessed the glomerular hemodynamic actions of RLX when administered acutely (75 min; 0.89 µg/100g body weight/hr, iv) and chronically (1.5µg/100g body weight/hr, sc). Both acute and chronic RLX produced marked renal vasodilation and increased renal plasma flow (RPF) in euvolemic, anesthetized male rats. GFR also increased with RLX but the magnitude of the rise was much less than the increase in RPF, due to concomitant falls in filtration fraction (FF). The fall in FF was the result of significant falls in glomerular blood pressure (P_GC) which occurred despite a slight rise in mean arterial blood pressure (MAP) with acute RLX, and no net change in MAP with chronic RLX. This fall in P_GC occurred because of the "in-series" arrangement of the afferent and efferent arteriolar resistance vessels (RA and RE) which can regulate P_GC independently of MAP. With both acute and chronic RLX RE relaxed to a greater extent than RA, thus producing falls in P_GC. Based on this finding, RLX has a beneficial hemodynamic impact on the kidney, which together with the antifibrotic actions suggest a strong therapeutic potential for use in CKD.

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