The heart is the first organ to form during embryogenesis, and heart formation is essential for subsequent embryonic development. Since the identification of a cardiac-restricted transcription factor Csx/Nkx-2.5 in the early 1990s, extensive studies on cardiac development have been done in various species ranging from flies to humans. Molecular dissection of regulatory pathways that control multiple steps of cardiogenesis will not only advance our understanding of cardiac development and congenital heart diseases, but will also provide an important clue to novel therapeutic strategies for heart diseases.

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We have reported that the contractility index (E_max) and the total mechanical energy (PVA) of arrhythmic beats of the left ventricle (LV) distribute normally in canine hearts under electrically induced atrial fibrillation (AF). Here, E_max is the ventricular elastance as the slope of the end-systolic (ES) pressure-volume (P-V) relation (ESPVR), and PVA is the systolic P-V area as the sum of the external mechanical work within the P-V loop and the elastic potential energy under the ESPVR. To obtain E_max and PVA, we had to assume the systolic unstressed volume (V_o) as the V-axis intercept of the ESPVR to be constant despite the varying E_max, since there was no method to obtain V_o directly in each arrhythmic beat. However, we know that in regular stable beats V_o decreases by ∼7 ml/100 g LV with ∼100 times the increases in E_max from ∼0.2 mmHg/(ml/100 g LV) of almost arresting weak beats to ∼20 mmHg/(ml/100 g LV) of strong beats with a highly enhanced contractility. In the present study, we investigated whether E_max and PVA under AF could still distribute normally, despite such E_max-dependent V_o changes. The present analyses showed that the E_max changes were only ∼3 times at most from the weakest to the strongest arrhythmic beat under AF. These changes were not large enough to affect V_o enough to distort the frequency distributions of E_max and PVA from normality. We conclude that one could practically ignore the slight E_max and PVA changes with the Emax-dependent V_o changes under AF.

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The reflex effects of noxious mechanical stimulation of a hindpaw or abdominal skin on ovarian blood flow, and the reflex pathways involved in those responses were examined in anesthetized rats. Blood flow in the left ovary was measured using a laser Doppler flowmeter, and the activity of the left ovarian sympathetic nerve and mean arterial pressure (MAP) of the common carotid artery were recorded. Stimulation of the left or right hindpaw for 30 s produced marked increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the left ovarian sympathetic nerves were severed, the same stimulus produced a remarkable monophasic increase in ovarian blood flow that was explained by passive vasodilation due to a marked increase in MAP. After spinal transection at the third thoracic (T3) level, the responses of MAP, ovarian sympathetic nerve activity, and ovarian blood flow to hindpaw stimulation were nearly abolished. Stimulation of the abdomen at the right or left side for 30 s produced slight increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the ovarian sympathetic nerves were severed, the response of the ovarian blood flow changed to a monophasic increase due to an increase in MAP. After spinal transection, stimulation of the left abdomen produced a moderate increase in MAP, a remarkable increase in ovarian sympathetic nerve activity and a slight decrease in ovarian blood flow during the stimulation. In contrast, stimulation of the right abdomen produced a smaller response in ovarian sympathetic nerve activity during the stimulation while it increased the MAP to a similar degree. Ovarian blood flow slightly increased after the end of stimulation, which was explained as passive vasodilation due to the increase in MAP. In conclusion, stimulation of somatic afferents affects ovarian blood flow by inducing changes in ovarian sympathetic nerve activities and blood pressure. When stimulation was applied to a hindpaw whose segment of afferent input is far from the segment of the ovarian sympathetic nerves, it took a supraspinal reflex pathway. However, when stimulation was applied to the abdomen whose spinal segment of the afferent is close to the segment of the ovarian sympathetic nerve output, there are spinal segmental reflex pathways. The present results demonstrate that spinal reflexes depend on the laterality of the stimulus, while supraspinal reflexes do not depend on the laterality of the stimulus.

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This study examined the effects of whole-body vibration (WBV) on the hormone and lipolytic responses. Eight male subjects performed WBV and control (CON) trials on separate days. The WBV session consisted of 10 sets of vibration for a duration of 60 s with rest periods of 60 s between each set (frequency 26 Hz). The subjects maintained a static squat position with knees bent on the platform. In the CON trial, the WBV stimulation was not imposed. Blood samples were collected before both trials and during the recovery period. In the WBV trial, the concentrations of plasma epinephrine (Epi) and norepinephrine (NE) increased immediately after the session (P < 0.05). Serum free fatty acids (FFA) concentration increased significantly at the 150, 180, and 210 min points of the recovery period in the WBV trial (P < 0.01) with the interaction between trial and time (P < 0.01). Serum glycerol showed no significant change in either trial. These results suggest that the WBV session causes secretions of Epi and NE, and it subsequently increases FFA concentration during the recovery period. However, because the FFA response was inconsistent with that of glycerol, we were unable to clarify the effect of WBV exposure on lipolysis.

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In mammals, including humans, a brain-gut hormone, cholecystokinin (CCK) mediates the satiety effect via CCK-A receptor (R). We generated CCK-AR gene-deficient (−/−) mice and found that the daily food intake, energy expenditure, and gastric emptying of a liquid meal did not change compared with those of wild-type mice. Because CCK-AR(−/−) mice show anxiolytic status, we examined the effects of restraint stress. Seven hours of restraint stress was found to significantly decrease both body weight and food intake during the subsequent 3 days in all tested animals. On the fourth day after restraint stress, the CCK-AR(−/−) mice showed a significantly higher level of daily food intake than prior to stress, and food intake recovered to prestress levels in the wild-type mice. Since peripheral CCK-AR has been known to mediate gastric emptying, both gastric emptying and gastric acid secretion were determined to examine the mechanism of overeating in CCK-AR(−/−) mice. Neither gastric emptying nor gastric acid secretion differed between CCK-AR(−/−) and wild-type mice on the fourth day after stress. In contrast, however, the contents of dopamine and its metabolites in the cerebral cortex of CCK-AR(-/-) mice were increased by stress, but were rather decreased in wild-type mice. Changes in 5-hydroxytryptamine (5-HT) and its metabolite 5HIAA did not differ between the genotypes. In conclusion, CCK-AR(−/−) mice showed overeating after restraint stress, and dopaminergic hyperfunction in the brain of these mice was observed. The present evidence suggests that the CCK-AR function, possibly via altering the dopaminergic function, might be involved in overeating after stress.

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The roles of cyclooxygenase (COX) and prostaglandins (PGs) in the regulation of vasoreactivity of rat gingival arterioles in vivo were evaluated by sing an intravital microscope. The superfusion of indomethacin (a nonselective COX inhibitor) or SC-560 (a selective COX-1 inhibitor) onto the gingiva significantly constricted the arterioles, though NS-398 (a selective COX-2 inhibitor) did not affect the diameter of the arterioles. The SC-560–mediated constriction of the arterioles was completely reversed by an additional treatment with arachidonic acid (AA). The superfusion of AA, beraprost-Na (an analogue of PGI2) or PGE2 onto the gingival significantly dilated the arterioles dose-dependently. The AA-induced dilation of the arterioles was significantly reduced by the treatment with SC-560 or NS-398. The expression of COX-1 and COX-2 were positive in the endothelium, but not the smooth muscles, of the arterioles. The expression of PGE synthase (PGES) was found only in the smooth muscles, but not the endothelium, of the arterioles. Neither the endothelium nor the smooth muscles of the arterioles expressed PGI synthase (PGIS). These findings suggest that the COX-2–mediated PG cascade may collaborate with the COX-1 pathway in the regulation of arteriolar myogenic activity in rat gingiva in the case of the supply of a large amount of AA.

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It remains controversial which of the two regulators, red blood cell velocity (RBC-V) or concentration (RBC-C), is a main contributor to increasing flow (RBC-F) during functional hyperemia in the rat hippocampus induced by N-methyl-D-aspartate (NMDA). To address this, we monitored these parameters simultaneously under NMDA-infusion via microdialysis in the hippocampus of urethane-anesthetized rats and found a greater elevation in RBC-V than in RBC-C. This suggests that an RBC-V-dependent increase in RBC-F occurs under NMDA-induced functional hyperemia in the hippocampus as well as in the cortex.

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