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

The involvement of adrenergic signaling and sarcoplasmic calcium regulatory proteins in the development of heat acclimation-induced adaptations in car diac mechanics was studied in heat-acclimated (34 degrees C) rats for 2, 5, and 30 days (AC(2), AC(5), and AC(30), respectively). Control (C) rats wer e held at 24 +/- 1 degrees C. Systolic pressure (LVP) and velocities of con traction (dP/dt/P) and relaxation (2dP/dt/P) were measured using a Langendo rff 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 p roteins, steady-state levels of Ca2+-ATPase and phospholamban (PLB) mRNAs a nd the encoded proteins Ca2+-ATPase [sarco(endo)plasmic reticulum Ca2+-ATPa se (SERCA)] and PLB were measured using semiquantitative RT-PCR and Western immunoblotting, respectively. Both short (STHA; AC(2) and AC(5))- 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 p arameters decreased (P < 0.05), implying decreased velocity of contraction and relaxation. beta-AR density remained unchanged with their affinity mark edly decreased (P < 0.05). AR responsiveness, however, diminished in AC(2) but was markedly enhanced on LTHA. During STHA, PLB and sarcoplasmic reticu lum Ca2+-ATPase transcripts were upregulated with no change in the encoded proteins except for SERCA downregulation on AC(5), 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 downre gulation of SERCA and upregulation of PLB. Our data fit a biphasic acclimat ion model in which desensitized adrenergic signaling is dominant during STH A, whereas on LTHA, the contractile machinery is influenced by altered expr ession of the calcium regulatory proteins leading to both augmented adrener gic inotropic response (via PLB elevation) and decreased velocity of relaxa tion. The sustained low thyroxin measured on LTHA causally associates with this response.