Alteration in myofilament response to Ca²⁺is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca²⁺are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca²⁺sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca²⁺. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca²⁺- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca²⁺-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca²⁺sensitivity are able to diminish the effect of I/R on cardiac function.

Although it has been suggested that vasopressin (VP) acts within the central nervous system to modulate autonomic cardiovascular controls, the mechanisms involved are not understood. Using nonpeptide, selective V_1a, V_1b, and V₂ antagonists, in conscious rats, we assessed the roles of central VP receptors, under basal conditions, after the central application of exogenous VP, and after immobilization, on cardiovascular short-term variability. Equidistant sampling of blood pressure (BP) and heart rate (HR) at 20 Hz allowed direct spectral analysis in very-low frequency (VLF-BP), low-frequency (LF-BP), and high-frequency (HF-BP) blood pressure domains. The effect of VP antagonists and of exogenous VP on body temperature (T_b) was also investigated. Under basal conditions, V_1a antagonist increased HF-BP and T_b, and this was prevented by metamizol. V_1b antagonist enhanced HF-BP without affecting T_b, and V₂ antagonist increased VLF-BP variability which could be prevented by quinapril. Immobilization increased BP, LF-BP, HF-BP, and HF-HR variability. V_1a antagonist prevented BP and HR variability changes induced by immobilization and potentiated tachycardia. V_1b antagonist prevented BP but not HR variability changes, whereas V₂ antagonist had no effect. Exogenous VP increased systolic arterial pressure (SAP) and HF-SAP variability, and this was prevented by V_1a and V_1b but not V₂ antagonist pretreatment. Our results suggest that, under basal conditions, VP, by stimulation of V_1a, V_1b, and cognate V₂ receptors, buffers BP variability, mostly due to thermoregulation. Immobilization and exogenous VP, by stimulation of V_1a or V_1b, but not V₂ receptors, increases BP variability, revealing cardiorespiratory adjustment to stress and respiratory stimulation, respectively.

Effects of V₁ (OPC-21268) and V₂ (OPC-31260) vasopressin antagonists on blood pressure (BP) short-term variability were investigated in adult spontaneously hypertensive rats (SHR) under basal conditions and after the stimulation of vasopressin release by hemorrhage. BP was recorded intra-arterially and sampled at 20 Hz to be analyzed on a personal computer. BP time spectra were calculated on 30 stationary overlapping 2048 point-time series. Spectral power was estimated in total (0.00976 – 3 Hz), very low frequency (VLF: 0.00976 – 0.195 Hz), low frequency (LF: 0.195 – 0.605 Hz), and high frequency (HF: 0.8 – 3 Hz) regions. Under basal conditions a V₁ antagonist (5 mg/kg, i.v.) decreased BP without affecting BP variability, while combined (V₁ + V₂) blockade or V₂ blockade (1 mg/kg, i.v.) alone did not affect cardiovascular parameters. Mild hemorrhage (5 ml/kg per min) increased HF-BP variability, while moderate (10 ml/kg per min) and massive (15 ml/kg per min) hemorrhage did not affect it. In V₁, but not V₂, antagonist pre-treated SHR HF-BP increased significantly after moderate and massive hemorrhage. V₁ or V₂ antagonist pre-treatment also enhanced VLF-BP variability during massive hemorrhage. Moreover V₁ blockade prevented hemorrhage-induced bradycardia, while V₂ blockade potentiated it. It follows that in adult SHR, vasopressin buffers BP oscillations in HF and VLF frequency domains only in hypovolaemic conditions and that the modulation of the autonomic adjustment of the HR to hemorrhage by vasopressin is preserved.