Mechanism underlying the negative inotropic effect in rat left ventricle in hyperthermia: the role of TRPV1

Figures

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  Fig. 1. Effects of capsazepine (CPZ) in simultaneous recordings of blood pressure of a support rat; perfusion pressure (BP), left ventricular pressure (LVP), arteriovenous oxygen content difference (AVO2D), coronary blood flow (CBF), and circulatory blood temperature (Temp) at midrange left ventricular volume (mLVV) during heating at 42 °C in the absence (a) or presence of CPZ (b) in an excised, cross-circulated rat heart preparation. The open arrow in the left panel (a) indicates that the value of end-systolic pressure (ESP) on LVP gradually decreased from 146 to 110 mmHg until 42 °C after onset of heating, which was partially suppressed by the infusion of CPZ (approximately 1.23 µg/mL in blood) (b)

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  Fig. 2. Representative data of LV end-systolic pressure–volume relation (ESPVR), LV end-diastolic pressure–volume relation (EDPVR), and myocardial oxygen consumption per beat (VO2)-systolic pressure–volume area (PVA) relation in the presence of CPZ (1.59 µg/mL in blood) during 42 °C (a and b, dotted lines) and in the presence of capsaicin (Cap) (0–461 ng/mL in blood) at 37 °C (c and d, dotted lines), respectively. The arrows in panel A indicate that the decrease in LV ESP at mLVV at 42 °C (solid triangle) was partially inhibited by CPZ (open square). The fine line indicates the estimated LV ESPVR at 42 °C. Thus, the VO2–PVA data point at mLVV in CPZ-treated heart at 42 °C (solid square) shifted right-downward from that in hyperthermia-heart (solid triangle), which left-downward shifted data point from it at 37 °C (solid circle) (b). On the other hand, the LV ESPVRs in Cap-treated heart shifted downward (c) and each PVA and VO2 values (open triangles) at each LVV during Cap infusion (230 ng/mL in blood) was smaller than each control value (solid circles), and the VO2–PVA linear relations during Cap infusion shifted downward; VO2-intercept values decreased without changes in the slope (d).…

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  Fig. 3. Comparison of the mean slope (oxygen cost of PVA; a), mean VO2 intercept (PVA-independent VO2; b), mean VO2 consumed in E–C coupling (c), mean basal metabolic VO2 (d), mean ESP at mLVV (e), and mean CBF at mLVV (f) in the presence or absence of Cap or CPZ at 37 °C or 42 °C. Group data are mean ± SD. *p < 0.05 vs. 37 °C,†p < 0.05 vs. 42 °C. The mean slope and mean CBF did not change in Cap- or CPZ-treated hearts during 37 °C or 42 °C (a, f). The mean VO2 intercepts in Cap-treated hearts were significantly lower than that at 37 °C (b), which was due to the decrease in mean VO2 consumed in E–C coupling (c) without changing mean basal metabolic VO2 (d). The decrease in the mean VO2 for E–C coupling and the increase of mean basal metabolic VO2 in hyperthermia-hearts without changing mean VO2 intercepts was inhibited by CPZ-treatment (c, d). The mean ESP at mLVV in hyperthermia- and Cap-treated hearts were significantly lower than that during 37 °C (e). The decrease of mean ESP at mLVV in hyperthermia-hearts significantly inhibited by CPZ-treatment (e)

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  Fig. 4. Western blot analysis of total phospholamban (PLB), phosphorylated phospholamban on Ser16 (p-PLB Ser16) and Thr17 (p-PLBThr17), and GAPDH in LV tissues of the presence or absence of Cap or CPZ at 37 °C or 42 °C. Representative data of total PLB, p-PLB Ser16, and p-PLBThr17 (a). Comparison of the mean protein levels of total PLB/GAP (b), p-PLBSer16/PLB (d), and p-PLBThr17/PLB (c). Values are mean ± SD of 5–6 LV tissues for each experimental group. *p < 0.05 vs. 32 °C,†p < 0.05 vs. 42 °C

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  Fig. 5. Representative data of LV pressure–time curves (a, d), normalized of LV pressure–time curves (b, e), and logistic time constants (c, f) at mLVV in the presence or absence of Cap or CPZ during 37 °C or 42 °C. Values are mean ± SD of six LV pressure–time curves at mLVV for each experimental group (c, d). *p < 0.05 vs. 37 °C,†p < 0.05 vs. 42 °C