Triiodothyronine enhances inotropic effects of angiotensin II in non failing myocytes

BACKGROUND: Subclinical thyrotoxicosis, caused by thyroid hormone treatment or by endogenous thyroid disease, may be associated with increased cardiac contractility and diastolic dysfunction. The cardiac effects of chronic hyperthyroidism is known to occur through triiodothyronine (T3)-mediated synthesis of specific proteins. However, more recent studies suggested that T3 may increase cardiac performance acutely, independent of protein neosynthesis even if it is still debated whether triiodothyronine (T3) has direct effects on myocyte contractile performance. Therefore this study was designed to investigate whether T3 acts directly on myocyte itself or is able to affect the procontractile response of beta-adrenergic or angiotensin II receptor stimulation. METHODS: To assess the mechanical effect of T3 at the cellular level, adult rat ventricular myocytes were isolated and stimulated to contract at 1 Hz (24°C). The effects of increasing T3 concentrations (10-12 to 10-8 M) on peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocities of shortening/relengthening (+/-dL/dt) were assessed with an IonOptix SoftEdge system. In separate sets of experiments the effects of T3 (10-6 M) on the contractility of myocytes perfused with isoproterenol (10-9 to 10-6 M) or Ang II (10-9 to 10-6 M) for 10 min were investigated. RESULTS: Acute administration of T3 (10 nM) did not cause any change in myocyte shortening extent, shortening velocity, and lenghtening velocity. Isoproterenol 100 nM significantly increased peak shortening (p<0.001), shortening velocity (p<0.006) and lenghtening velocity (p<0.002) but those parameters were not significantly affected by the contemporary presence of T3. Ang II caused a significant increase in peak shortening (p<0.025) which was furtherly enhanced in the presence of T3 (p<0.027). CONCLUSIONS: These results seem to indicate that the reported effects of T3 on myocardial contractility are not due to a direct cardiac contractile action at the single ventricular myocyte level.