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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/d t/P) and relaxation (−dP/d t/P) were measured using a Langendorff system. For adrenergic signaling, β-adrenoreceptor (AR) density and affinity (Scatchard plots) and cardiac inotropic response to norepinephrine (10−7mM, ± 10−6mM 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; AC2and AC5)- and long-term heat acclimation (LTHA; AC30) enhanced LVP. However, dP/d t ⋅ P and −dP/d t ⋅ 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. β-AR density remained unchanged with their affinity markedly decreased ( P < 0.05). AR responsiveness, however, diminished in AC2but 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.

Heat acclimation (AC) improves cardiac mechanical and metabolic performance. Using cardiomyocytes and isolated hearts from 30-day and 2-day acclimated rats (AC and AC-2d, 34°C), we characterized cellular contractile mechanisms under normothermic (37°C) and hyperthermic (39–42°C) conditions. To determine contractile responses, Ca2+transients (Ca2+T), sarcoplasmic reticulum (SR) Ca2+pool size (fura-2/indo-1 fluorescence), force generation [amplitude systolic motion (ASM)], L-type Ca2+channels [dihydropyridine receptor (DHPR)], ryanodine receptors (RyRs), and total (PLBt) and phosphorylated phospholamban [serine phosphorylated (PLBs) and theonine phosphorylated (PLBtr)] proteins and transcripts were measured (Western blot, RT-PCR). Cardiac mechanical performance was measured using a Langendorff system. We demonstrated that AC and AC-2d increased Ca2+T amplitude (148% and 147%, respectively) and twitch force (180% and 130%, respectively) and desensitized myofilaments, as indicated by a rightward shift in the ASM-Ca2+relationships, despite no change in SR Ca2+pool size. Hence, generation of higher Ca2+T underlies greater force development in AC and AC-2d myocytes. In isolated hearts, ryanodine administration eliminated differences between AC and control (C) hearts, implying an important role for RyRs in that acclimation phase. Increased expression of DHPR and RyRs, and decreased PLBs/PLBt in AC hearts only, suggest that different pathways increase force generation in the AC-2d vs. AC myocytes. At basal beating rates, hyperthermia (39–41°C) enhanced pressure generation in AC hearts. C hearts failed to restitute pressure beyond 39°C. Increased beating frequency produced negative inotropic response. In C cardiomyocytes, hyperthermia elevated basal cytosolic Ca2+and tension, Ca2+T, and ASM. AC myocytes enhanced Ca2+T but showed myofilament desensitization, suggesting its involvement in cardiac protection against hyperthermia. Collectively, both Ca2+turnover and myofilament responsiveness are important adaptive acclimatory targets during normothermic and hyperthermic conditions.

Skin blood flow and microvascular resistance were measured in the feet of hypertensive and normotensive subjects by the non-invasive transient thermal clearance method. Skin blood flow decreased and microvascular resistance increased as a function of systolic brachial blood pressure for the non-diabetic subjects who were not treated by vasoactive medication. The relationship between blood flow and systolic blood pressure for diabetic patients and for patients who were treated by enalapril was poor. The average resistance for non-diabetic patients treated by enalapril was lower than that of untreated non-diabetic subjects. For diabetic patients no significant difference in resistance between enalapril treated and untreated patients was found. The results demonstrate that for non-diabetic patients the role of microvascular resistance in hypertension is significant while it is less important in diabetic patients.