The physiological regulation of renal Pi reabsorption is mediated by renal type II Na/Pi cotransporters (type IIa and type IIc). The type IIa transporter is regulated, among other factors, by dietary Pi intake and parathyroid hormone (PTH). The PTH-induced inhibition of Pi reabsorption is mediated by endocytosis of the type IIa transporter from the brush-border membrane and subsequent lysosomal degradation. Type IIa is part of the heteromeric protein complexes organized by PDZ proteins. Furthermore, during Pi depletion the type IIc Na/Pi cotransporter is induced in the apical membrane of proximal tubular cells. The type IIc transporter is also regulated by PTH via internalization, but by a vesicular transport pathway distinct from that used by the type IIc transporter. Studying the mechanisms of type IIa and type IIc transporters has increased the understanding of the control of proximal tubular Pi handling and thus of overall Pi homeostasis.

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The efficiency from the ventricular O₂ consumption (VO₂) to the total mechanical energy (TME) generated by ventricular contraction has proved relatively constant at ∼35%, independent of the loading and contractile conditions in a canine heart. TME is the sum of the external mechanical work for ejecting a stroke volume against the afterload and of the mechanical potential energy for developing ventricular pressure in each beat. The ∼35% VO₂-to-TME efficiency indicates an also constant ∼60% ATP-to-TME efficiency in a beating heart, based on the nominal ∼60% VO₂-to-ATP efficiency in the myocardial oxidative phosphorylation. I newly attempted to explain the load-independent ∼60% ATP-to-TME efficiency by the recently reported ∼7–10 nm unitary step size and ∼0.8–1.5 pN unitary force of a cross-bridge (CB) at the molecular level in in vitro motility assays. This single CB behavior suggests that its unitary cycle could generate a mechanical energy of ∼0.6–1.5×10⁻²⁰ J at most. From the nominal free energy of ∼10×10⁻²⁰ J per ATP, the efficiency from one ATP to the CB unitary cycle would then be ∼6–15%. This low efficiency is only ∼1/10–1/4 of the ∼60% ATP-to-TME efficiency at the heart level. This discrepancy suggests that each CB would repeat the unitary cycle at least ∼4–10 times per ATP to achieve the high constant ATP-to-TME efficiency in a beating heart. This seems to represent a considerable mechanoenergetic advantage of the heart at the integrative heart level as compared to the molecular CB level.

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Since O₂ is the bare necessity for multicellular organisms, they develop multiple protective mechanisms against hypoxia. Mammals will adapt to hypoxia in short and long terms. The short-term responses include enhancement of the respiratory and cardiac functions, adrenaline secretion from adrenal medullary cells, and pulmonary vasoconstriction, whereas the long-term response is the increase in erythropoietin production with the consequent increase in red blood cells. Although much work has been done to elucidate molecular mechanisms for O₂-sensing for the last ten years, the majority of the mechanisms remain unclear. We will review mechanisms proposed for hypoxia detection in carotid body type I cells, pulmonary artery smooth muscle, adrenal medullary cells, and liver cells, with the special focus on adrenal medullary cells.

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The aim of this study was to determine the energetic factors of middle-distance running performance in junior elite runners according to gender and by using measurements from on-track performances. Fifteen elite runners (8 males and 7 females) were investigated by means of an incremental test and an all-out run over 600 m performed with a 2-d interval. We calculated (1) the aerobic maximal power (E_{r max aero}, in W kg⁻¹), including VO_{2 max} and the delay of attainment of VO_{2 max} in the 600 m run; (2) the anaerobic power (E_{r max anaero}), i.e., the oxygen deficit (J kg⁻¹) divided by the duration of the 600 m run. Despite the difference in race duration (87 ± 3 vs. 102 ± 2 s), the 600 m run was made at the same relative value of the velocity associated with VO_{2 max} (vVO₂ max) in males and females (121.6 ± 7 vs. 120 ± 8% VO_{2 max}, p = 0.7). E_{r max aero} explained most of the variance in the performance (the personal best performed 8 weeks later) between genders: 65 and 79% over 800 m (T₈₀₀) and 1,500 m (T_1,500). For females, E_{r max aero} explained most of the variance of T_1,500 (r² = 0.66), and E_{r max anaero} improved this prediction (r² = 0.84). No energetic factor predicted the performance on 800 m run in males. In elite junior athletes, the energetic model with individual data measured over an all-out 600 m performed on a track, provides an explanation for most of the variance in middle-distance running performances between genders. The distinction between aerobic power and anaerobic power allowed an improvement in the prediction of middle-distance running performances.

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Nociceptive cutaneous stimulation produces a reflex tachycardiac response that is mediated through the activation of cardiac sympathetic efferents. This response includes reflex components of both supraspinal and spinal origin, depending on which segmental afferent area is stimulated (for a review see Sato et al.: Rev Physiol Biochem Pharmacol 130: 1–328, 1997). We herein examined the effects of aging on these supraspinal and spinal reflexes in anesthetized rats that were 4–7 (young adult), 24–27 (old), and 32–36 (very old) months of age. In central nervous system (CNS)–intact animals, we found that the supraspinal tachycardiac response induced by the pinching of a hindpaw was well preserved in old rats but was significantly attenuated in very old rats, while pinching-induced increases in cardiac sympathetic nerve activity were well maintained in both of these rat populations. In spinalized animals, spinal-mediated changes in heart rate (HR) and cardiac sympathetic nerve activity induced by the pinching of the chest skin were well preserved in both old and very old rats. There were no significant differences in resting HR among the 3 age groups studied, though the maximum HR induced by the β-adrenergic agonist isoproterenol was reduced with age. The β-receptor–mediated maximum HR was greater than that induced by pinching in young adult and old rats, CNS-intact and spinalized rats, and very old spinalized rats, while the maximum HR was nearly the same as the pinching-induced HR in CNS-intact very old rats. These results suggest that both supraspinal and spinal neural reflex pathways involved in the cardiac sympathetic response to cutaneous pinching are well preserved in older animals. They also suggest that the decline in the responsiveness of the heart to β-adrenergic stimulation results in a reduced pinching-induced supraspinal tachycardiac response in very old rats.

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We investigated whether ischemic preconditioning (PC) attenuates ischemia/reperfusion-induced injury in part by decreasing apoptosis and whether tyrosine kinase (TK) can regulate the signaling pathway leading to apoptosis in delayed cardioprotection. Six groups of rabbits were studied in the early phase (EP) and in the delayed phase (DP): (1) sham-operated control animals were received vehicle only (Veh-sham); (2) rabbits that received I.V. genistein (a nonspecific TK inhibitor) 10 min before ischemia (Gen-sham); (3) rabbits that received I.V. daidzein (an inactive structural analog of genistein) 10 min before ischemia (Dzn-sham); (4) rabbits preconditioned with 4 cycles of 5-min occlusion of left anterior descending coronary artery (LAD) and 10-min reperfusion (PC); (5) rabbits that received I.V. genistein, 10 min before PC (Gen-PC); (6) rabbits that received I.V. daidzein 10 min before PC (Dzn-PC). All rabbits underwent 30-min ischemia followed by 180-min reperfusion. Infarct size in the PC, Gen-PC, and Dzn-PC groups in the EP was significantly (p < 0.0001) reduced relative to controls Gen and Dzn. Delayed cardioprotection was blocked significantly (p < 0.0001) by genistein. In the EP, apoptosis was significantly (p < 0.0001) decreased in PC, Gen-PC, and Dzn-PC groups relative to controls Gen and Dzn. In the DP, a reduction of apoptosis was not seen in the Gen-PC group. This study suggests that PC reduces ischemic injury in part by decreasing apoptosis after ischemia/reperfusion and also that TK phosphorylation is involved in the signal transduction cascade leading to the decline of apoptosis in the DP.

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To investigate whether the Model-flow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to 4.8 ± 0.5 l/min, from 5.8 ± 0.6 l/min, during the postural change and increased to 12.8 ± 1.3 l/min during a stepping exercise, returning to 5.1 ± 0.4 l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from 0.737 to 1.588 among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure.

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The feasibility of precise mapping was investigated noninvasively on the face component in predominantly unilateral primary somatosensory cortices (SI) in six healthy subjects. We recorded somatosensory evoked magnetic fields (SEFs) from the SI and secondary somatosensory cortices (SII) following the electrical stimulation of six skin sites: the infraorbital foramen, the angle of mouth, the upper lip, the lower lip, the mental foramen, and the mandibular angle. The median nerve at the wrist was stimulated as a standard of the map. The location of the equivalent current dipoles (ECDs) estimated from the distribution of magnetic fields was identified on MR images of the brain on each subject. The ECDs of the early components of SEF with peaks of 20–30 ms aligned along the SI in the hemisphere contralateral to the stimulation site. Late components with peaks of 80–150 ms were recorded from the bilateral hemispheres, and their ECDs were identified in the SII of the bilateral hemispheres. There was a distinct separation between the ECD locations representing discrete sites on the face and thumb in the SI of the contralateral hemisphere. Five sites of the face area in SI at the contralateral hemisphere were compatible with the conventional arrangement of homunculus in one subject. However, the remaining subjects had variations in the arrangement. The face area reorganization in the SI is possible to be related to the use-dependent cortical plasticity of the individual or to the perceptual experience by vision and proprioception.

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We examined the effects of chronic intermittent hypoxia (IH) on the hemodynamics of systemic circulation in rat. Chronic IH has no effect on the hemodynamics in the normoxia condition, but it could effectively prevent the fall of hemodynamics during acute hypoxia.

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