| First Author | Kilić A | Year | 2007 |
| Journal | Endocrinology | Volume | 148 |
| Issue | 9 | Pages | 4162-9 |
| PubMed ID | 17510245 | Mgi Jnum | J:129491 |
| Mgi Id | MGI:3769329 | Doi | 10.1210/en.2007-0182 |
| Citation | Kilic A, et al. (2007) Local actions of atrial natriuretic peptide counteract angiotensin II stimulated cardiac remodeling. Endocrinology 148(9):4162-9 |
| abstractText | The cardiac hormones atrial and brain natriuretic peptides (NPs) counteract the systemic, hypertensive, and hypervolemic actions of angiotensin II (Ang II) via their guanylyl cyclase-A (GC-A) receptor. In the present study, we took advantage of genetically modified mice with conditional, cardiomyocyte (CM)-restricted disruption of GC-A (CM GC-A knockout mice) to study whether NPs can moderate not only the endocrine but also the cardiac actions of Ang II in vivo. Fluorometric measurements of [Ca(2+)](i) transients in isolated, electrically paced adult CMs showed that atrial NP inhibits the stimulatory effects of Ang II on free cytosolic Ca(2+) transients via GC-A. Remarkably, GC-A-deficient CMs exhibited greatly enhanced [Ca(2+)](i) responses to Ang II, which was partly related to increased activation of the Na(+)/H(+)-exchanger NHE-1. Chronic administration of Ang II to control and CM GC-A knockout mice (300 ng/kg body weight per minute via osmotic minipumps during 2 wk) provoked significant cardiac hypertrophy, which was markedly exacerbated in the later genotype. This was concomitant to increased cardiac expression of NHE-1 and enhanced activation of the Ca(2+)/calmodulin-dependent prohypertrophic signal transducers Ca(2+)/calmodulin-dependent kinase II and calcineurin. On the basis of these results, we conclude that NPs exert direct local, GC-A-mediated myocardial effects to antagonize the [Ca(2+)](i)-dependent hypertrophic growth response to Ang II. |
