Fig. 3: The NPR1 agonist antibody REGN5381 persistently reduces systolic BP in NPR1hu/hu mice in the absence of diuresis, and acts as a direct vasodilator.
From: Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone
a, Administration of a single subcutaneous dose of 1, 5, 25 or 50 mg per kg REGN5381 in normotensive NPR1hu/hu mice demonstrated marked reductions in systolic BP that were maintained for up to 28 days (black circles, REGN1945 (the immunoglobulin G4 isotype control), 25 mg per kg; pink squares, REGN5381, 1 mg per kg; blue triangles, REGN5381, 5 mg per kg; red triangles, REGN5381, 25 mg per kg; purple diamonds, REGN5381, 50 mg per kg). b, Post-dose assessments after administration of REGN5381 (red squares) or control monoclonal antibody (REGN1945; black circles) on urinary cGMP concentration and urine volume. c, Administration of REGN5381 induces greater venous dilation in precontracted ex vivo vessels from NPR1hu/hu mice, as evaluated in an ex vivo vessel ring assay (grey bars, isotype control, vein; black bars, acetylcholine, vein; white bars, acetylcholine, artery; blue bars, REGN5381, artery; red bars, REGN5381, vein). d, NPR1 expression is significantly higher in the femoral vein than in the femoral artery.
