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

Abstract

Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory actions that 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 [glomerular capillary pressure (P_GC)], which exacerbates progression of CKD, we assessed the glomerular hemodynamic actions of acute (0.89 µg·100 g body wt^-1·h^-1 iv over 75 min) and chronic (1.5 µg·100 g body wt^-1·h^-1 sc) administration of RLX. Both acute and chronic RLX produced marked renal vasodilation and increased renal plasma flow (RPF) in euvolemic, anesthetized male rats. Glomerular filtration rate also increased with RLX, but the magnitude of the rise was much less than the increase in RPF due to concomitant decreases in filtration fraction. The fall in filtration fraction was the result of significant decreases in P_GC, despite a slight increase 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, which can regulate P_GC independently of MAP. With both acute and chronic RLX, efferent arteriolar resistance vessels relaxed to a greater extent than afferent arteriolar resistance vessels, 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 of RLX, suggests a strong therapeutic potential for use in CKD.

Keywords: GFR; afferent and efferent arterioles; renal plasma flow.

Fig. 1.

Effects of long-term relaxin (RLX) administration on mean arterial blood pressure (MAP) and heart rate (HR) in conscious, chronically instrumented rats. Values are means ± SE. RLX was given at a rate of 1.5 µg·100 g body wt⁻¹·h⁻¹ for 10 days via an osmotic pump implanted subcutaneously. Control rats received vehicle. Statistical significance was determined by 1-way ANOVA for within-group experiments. *P < 0.05 vs. day 0. #P < 0.05 for RLX vs. vehicle on days 1–10 (by unpaired t-test).