| First Author | Roth DM | Year | 1999 |
| Journal | Circulation | Volume | 99 |
| Issue | 24 | Pages | 3099-102 |
| PubMed ID | 10377071 | Mgi Jnum | J:133194 |
| Mgi Id | MGI:3777911 | Doi | 10.1161/01.cir.99.24.3099 |
| Citation | Roth DM, et al. (1999) Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopathy. Circulation 99(24):3099-102 |
| abstractText | BACKGROUND: We tested the hypothesis that increased cardiac myocyte adenylyl cyclase (AC) content increases cardiac function and response to catecholamines in cardiomyopathy. METHODS AND RESULTS: Transgenic mice with cardiac-directed expression of AC type VI (ACVI) were crossbred with mice with cardiomyopathy induced by cardiac-directed Gq expression. Gq mice had dilated left ventricles, reduced heart function, decreased cardiac responsiveness to catecholamine stimulation, and impaired beta-adrenergic receptor (betaAR)-dependent and AC-dependent cAMP production. Gq/AC mice showed improved basal cardiac function in vivo (P=0.01) and ex vivo (P<0.0005). When stimulated through the betaAR, cardiac responsiveness was increased (P=0.02), and cardiac myocytes showed increased cAMP production in response to isoproterenol (P=0.03) and forskolin (P<0.0001). CONCLUSIONS: Increasing myocardial ACVI content in cardiomyopathy restores cAMP-generating capacity and improves cardiac function and responsiveness to betaAR stimulation. |
