Transgenic mice that overexpress human type 1 angiotensin II receptor (AT1R) in the heart develop cardiac hypertrophy. Previously, we have shown that in 6-mo AT1R mice, which exhibit significant cardiac remodeling, fractional shortening is decreased. However, it is not clear whether altered contractility is attributable to AT1R overexpression or is secondary to cardiac hypertrophy/remodeling. Thus the present study characterized the effects of AT1R overexpression on ventricular L-type Ca2+ currents ( ICaL), cell shortening, and Ca2+ handling in 50-day and 6-mo-old male AT1R mice. Echocardiography showed there was no evidence of cardiac hypertrophy in 50-day AT1R mice but that fractional shortening was decreased. Cellular experiments showed that cell shortening, ICaL, and Cav1.2 mRNA expression were significantly reduced in 50-day and 6-mo-old AT1R mice compared with controls. In addition, Ca2+ transients and caffeine-induced Ca2+ transients were reduced whereas the time to 90% Ca2+ transient decay was prolonged in both age groups of AT1R mice. Western blot analysis revealed that sarcoplasmic reticulum Ca2+-ATPase and Na+/Ca2+ exchanger protein expression was significantly decreased in 50-day and 6-mo AT1R mice. Overall, the data show that cardiac contractility and the mechanisms that underlie excitation-contraction coupling are altered in AT1R mice. Furthermore, since the alterations in contractility occur before the development of cardiac hypertrophy, it is likely that these changes are attributable to the increased activity of the renin-angiotensin system brought about by AT1R overexpression. Thus it is possible that AT1R blockade may help maintain cardiac contractility in individuals with heart disease.
miRNA‐21 and miRNA‐133b are decreased in hyperthyroidism‐induced cardiac hypertrophy – Critical role of Type 1 Angiotensin II receptor (AT1R)
