From molecular and cellular to integrative heat defense during exposure to chronic heat.

Heat acclimation induces adaptive changes that improve the ability to cope with extreme environmental heat. Acclimatory homeostasis is manifested by an expanded dynamic thermoregulatory span (TRS), reflected in the intact organism by a lower temperature threshold (T(sh)) for heat dissipation, and delayed T(sh) for thermal injury. This principle shares common adaptive features with each of the thermoregulatory effectors. In the splanchnic circulation, e.g. the TRS of the thermally induced vasomotor response increases due to greater cardiac output distribution to the splanchnic vasculature, thereby increasing circulatory reserves and delaying thermal injury. During short-term heat acclimation (STHA), accelerated autonomic excitability plays a major role in the control of body temperature. Acclimatory homeostasis, however, is achieved only following long-term heat acclimation (LTHA), and is characterized by increased thermal effector efficiency, namely [effector organ output/autonomic signal] ratio >1. Two acclimatory responses, derived from our data on the acclimating rat model, are discussed: (1) acclimation of the cholinergic-muscarinic signaling for water secretion in the submaxillary gland; and (2) acclimatory mechanisms for increased contractile efficiency in the heart. Our data indicate that increased efficiency upon LTHA develops by reprogramming of gene expression. A reduced thyroid hormone level is responsible for some of the molecular adaptive cascades. Delayed thermal injury observed upon acclimation is due to enhanced cytoprotective mechanisms of which the inducible heat shock protein (HSP) 72 kDa plays a major role. Our data indicate that heat acclimation predisposes the HSP molecular machinery to respond faster and increases the constitutive level of the protein. STHA is the time-window during which most LTHA adaptations are switched on.