Endogenous relaxin does not affect chronic pressure overload-induced cardiac hypertrophy and fibrosis.

The effect of endogenous relaxin on the development of cardiac hypertrophy, dysfunction, and fibrosis remains completely unknown. We addressed this question by subjecting relaxin-1 deficient (Rln1-/-) and littermate control (Rln1+/+) mice of both genders to chronic transverse aortic constriction (TAC). The extent of left ventricular (LV) remodeling and dysfunction were studied by serial echocardiography over an 8-wk period and by micromanometry. The degree of hypertrophy was estimated by LV weight, cardiomyocyte size, and expression of relevant genes. Cardiac fibrosis was determined by hydroxyproline assay and quantitative histology. Expression of endogenous relaxin during the course of TAC was also examined. In response to an 8-wk period of pressure overload, TAC mice of both genotypes developed significant LV hypertrophy, fibrosis, hypertrophy related gene profile, and signs indicating congestive heart failure when compared with respective sham controls. The severity of these alterations was not statistically different between the two genotypes of either gender. Relaxin mRNA expression was up-regulated, whereas that of its receptor was unchanged in the hypertrophic myocardium of wild-type mice. Collectively, the extent of pressure overload-induced LV hypertrophy, fibrosis, and dysfunction were comparable between Rln1+/+ and Rln1-/- mice. Thus, although up-regulated in its expression, endogenous relaxin had no significant effect on the progression of cardiac maladaptation and dysfunction in the setting of chronic pressure overload.