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Am J Physiol Regul Integr Comp Physiol 279: R77-R85, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 1, R77-R85, July 2000

Changes in cardiac mechanics with heat acclimation: adrenergic signaling and SR-Ca regulatory proteins

Eynan Mirit1, Chaya Gross1, Yonathan Hasin2, Aharon Palmon3, and Michal Horowitz1

1 Division of Physiology, 3 Department of Oral Biology and 2 Department of Cardiology, Faculties of Dental Medicine and Medicine, The Hebrew University, Jerusalem 91120, Israel

The involvement of adrenergic signaling and sarcoplasmic calcium regulatory proteins in the development of heat acclimation-induced adaptations in cardiac mechanics was studied in heat-acclimated (34°C) rats for 2, 5, and 30 days (AC2, AC5, and AC30, respectively). Control (C) rats were held at 24 ± 1°C. Systolic pressure (LVP) and velocities of contraction (dP/dt/P) and relaxation (-dP/dt/P) were measured using a Langendorff system. For adrenergic signaling, beta -adrenoreceptor (AR) density and affinity (Scatchard plots) and cardiac inotropic response to norepinephrine (10-7 mM, ± 10-6 mM propranolol) were measured. For the regulatory proteins, steady-state levels of Ca2+-ATPase and phospholamban (PLB) mRNAs and the encoded proteins Ca2+-ATPase [sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)] and PLB were measured using semiquantitative RT-PCR and Western immunoblotting, respectively. Both short (STHA; AC2 and AC5)- and long-term heat acclimation (LTHA; AC30) enhanced LVP. However, dP/dt · P and -dP/dt · P in STHA hearts resembled that of the controls, whereas on LTHA, both parameters decreased (P < 0.05), implying decreased velocity of contraction and relaxation. beta -AR density remained unchanged with their affinity markedly decreased (P < 0.05). AR responsiveness, however, diminished in AC2 but was markedly enhanced on LTHA. During STHA, PLB and sarcoplasmic reticulum Ca2+-ATPase transcripts were upregulated with no change in the encoded proteins except for SERCA downregulation on AC5, leading to an increased PLB/SERCA ratio (P < 0.05). This mismatched preacclimation lusitropic state on STHA and increased PLB/SERCA ratio was evident (P < 0.05) due to downregulation of SERCA and upregulation of PLB. Our data fit a biphasic acclimation model in which desensitized adrenergic signaling is dominant during STHA, whereas on LTHA, the contractile machinery is influenced by altered expression of the calcium regulatory proteins leading to both augmented adrenergic inotropic response (via PLB elevation) and decreased velocity of relaxation. The sustained low thyroxin measured on LTHA causally associates with this response.

phospholamban; thyroxin; cardiac performance; adrenergic responsiveness; acclimation dynamics


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