| First Author | Kim M | Year | 2013 |
| Journal | Nat Med | Volume | 19 |
| Issue | 5 | Pages | 567-75 |
| PubMed ID | 23542788 | Mgi Jnum | J:198358 |
| Mgi Id | MGI:5496464 | Doi | 10.1038/nm.3128 |
| Citation | Kim M, et al. (2013) GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med 19(5):567-75 |
| abstractText | Glucagon-like peptide-1 receptor (GLP-1R) agonists exert antihypertensive actions through incompletely understood mechanisms. Here we demonstrate that cardiac Glp1r expression is localized to cardiac atria and that GLP-1R activation promotes the secretion of atrial natriuretic peptide (ANP) and a reduction of blood pressure. Consistent with an indirect ANP-dependent mechanism for the antihypertensive effects of GLP-1R activation, the GLP-1R agonist liraglutide did not directly increase the amount of cyclic GMP (cGMP) or relax preconstricted aortic rings; however, conditioned medium from liraglutide-treated hearts relaxed aortic rings in an endothelium-independent, GLP-1R-dependent manner. Liraglutide did not induce ANP secretion, vasorelaxation or lower blood pressure in Glp1r(-/-) or Nppa(-/-) mice. Cardiomyocyte GLP-1R activation promoted the translocation of the Rap guanine nucleotide exchange factor Epac2 (also known as Rapgef4) to the membrane, whereas Epac2 deficiency eliminated GLP-1R-dependent stimulation of ANP secretion. Plasma ANP concentrations were increased after refeeding in wild-type but not Glp1r(-/-) mice, and liraglutide increased urine sodium excretion in wild-type but not Nppa(-/-) mice. These findings define a gut-heart GLP-1R-dependent and ANP-dependent axis that regulates blood pressure. |
