Keiko Morimoto

The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats.

1. We investigated the central role of corticotrophin‐releasing factor (CRF‐41) in psychological stress‐induced responses, including cardiovascular, thermoregulatory and locomotive activity in free‐moving rats. 2. Psychological stress was induced by cage‐switch stress. After rats were placed in the novel environment, blood pressure, heart rate, body temperature and locomotive activity significantly increased. The intracerebroventricular (I.C.V.) injection of alpha‐helical CRF(9‐41), a CRF‐41 receptor antagonist, significantly attenuated the stress‐induced hypertension, tachycardia, hyperthermia and increase in locomotive activity. However, in unstressed rats, the I.C.V. injection of alpha‐helical CRF(9‐41) had no effect on physiological parameters measured in this study. 3. In unstressed rats, the I.C.V. injection of CRF‐41 (1 microgram and 10 micrograms) increased blood pressure, heart rate, body temperature and locomotive activity in a dose‐dependent manner. The changes in these responses were quite similar to those observed during cage‐switch stress. 4. The results suggest that central CRF‐41 plays an important role in psychological stress‐induced hypertension, hyperthermia, tachycardia and increase in locomotive activity. However, it is likely that central CRF‐41 does not contribute to normal cardiovascular and body temperature regulation when rats are free from stress.

Possible involvement of prostaglandins in psychological stress-induced responses in rats.

1. We investigated the effect of pre‐treatment with intraperitoneal (I.P.) injection of indomethacin, an inhibitor of prostaglandin synthesis, on psychological stress‐induced responses including cardiovascular, thermoregulatory and hormonal responses in free‐moving rats. 2. Psychological stress was induced by cage‐switch stress. After the rats were placed in the novel environment, blood pressure, heart rate and body temperature significantly increased. Plasma levels of adrenocorticotrophic hormone (ACTH) and prostaglandin E2 were significantly higher 30 min after exposure to stress, in comparison to normal levels. 3. Pre‐treatment with I.P. indomethacin significantly suppressed the increases in body temperature induced by cage‐switch stress, but had no effect on increases in blood pressure and heart rate induced by this stress. Indomethacin also significantly suppressed the increases in the plasma levels of ACTH and prostaglandin E2 induced by cage‐switch stress. 4. The present results suggest that prostaglandins are involved in the development of hyperthermia and the ACTH response induced by psychological stress.

Diagnosis and quantitative evaluation of secundum-type atrial septal defect by transesophageal Doppler echocardiography.

Transesophageal echocardiography (horizontal sector scan) was performed in 11 patients with secundum atrial septal defect (ASD). In all 11 patients, transesophageal echocardiography presented the definite visualization of the defect and a clear laminar shunt flow that showed its 2 peaks in late systole and late diastole. We estimated the size of ASD and a shunt volume across the defect by using transesophageal echocardiography. The defect size determined by transesophageal echocardiography was correlated with the surgical measurement (horizontal width, r = 0.92, p less than 0.001; vertical length, r = 0.85, p less than 0.01). A significant high correlation was shown between the shunt volume measured by transesophageal echocardiography and that by Ficks method (r = 0.87, p less than 0.01). There was no significant correlation between the pulmonary to systemic flow volume (ratio) and the mean shunt flow velocity across ASD, although a high linear correlation was observed between the pulmonary to systemic flow ratio and the defect size in horizontal direction (r = 0.82, p less than 0.01). Transesophageal echocardiography used for diagnosis and quantitative evaluation of ASD could be performed easily and satisfactorily within 10 minutes. Thus, transesophageal echocardiography is a useful method in evaluation of the defect size and the shunt flow volume of ASD. The mean shunt flow velocity was not a reliable index for estimating the shunt flow volume. The defect size might be a valuable determinant of left-to-right shunt volume in ASD.

Cardiovascular responses induced in free-moving rats by immune cytokines.

1. We investigated the effect of intraperitoneal (I.P.) injections of the immune cytokines, interleukin‐1 beta (IL‐1 beta) and tumour necrosis factor (TNF) on cardiovascular responses in free‐moving rats, using a biotelemetry system. 2. The I.P. injection of a small dose of IL‐1 beta (1 microgram/kg) induced a monophasic increase in the heart rate, and that of a large dose (10 micrograms/kg) induced biphasic increases in the blood pressure and heart rate. However, the I.P. injection of any of several doses of TNF (1, 10 and 50 micrograms/kg) had no effect on cardiovascular responses in rats. 3. Pre‐treatment with I.P. injection of indomethacin (10 mg/kg), an inhibitor of cyclo‐oxygenase, significantly suppressed the cardiovascular responses and the increase in the plasma noradrenaline (NA) concentration induced by I.P. injection of IL‐1 beta. 4. Microinjection of IL‐1 beta (1 and 10 ng) into the preoptic and anterior hypothalamic (PO‐AH) region induced dose‐dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with I.P. indomethacin (10 mg/kg). In addition, microinjection of prostaglandin E2 (20 and 100 ng) into the PO‐AH region increased blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. 5. The present results suggest that IL‐1 beta stimulates the release of prostaglandins, presumably E series, near regions of the hypothalamus, which act on the hypothalamus to induce activation of the sympathetic nervous system. Subsequently, the blood pressure, heart rate and the plasma level of NA increase.

Does an increase in prostaglandin E2 in the blood circulation contribute to a febrile response in rabbits

We investigated the effect of intravenous injection of human recombinant interleukin-1 beta (IL-1) on rectal temperature and prostaglandin E2 concentration in venous and arterial blood and in the push-pull perfusate in the third ventricle of rabbits. Changes in plasma prostaglandin E2 concentration in blood obtained from the marginal ear vein paralleled changes in body temperature during both monophasic and biphasic fevers. The plasma concentration of prostaglandin E2 in blood obtained from the jugular vein increased during the first phase of the biphasic fever. However, no increase in the prostaglandin E2 level in the carotid arterial blood was observed during the biphasic fever. The levels of prostaglandin E2 in the push-pull perfusate in the third ventricle were markedly elevated during both monophasic and biphasic fevers. Intracarotid infusion of prostaglandin E2 did not produce a fever nor result in a change in the prostaglandin E2 concentration of the push-pull perfusate in the third ventricle. The present results suggest that prostaglandin E2 from the blood circulation does not contribute to fever production in rabbits.

ACTH release induced in rats by noradrenaline is mediated by prostaglandin E2.

1. We investigated the involvement of prostaglandin E2 in the development of the adrenocorticotrophic hormone (ACTH) response induced by noradrenaline (NA) in rats. 2. Intravenous (i.v.) injection of NA produced dose‐dependent increases in the plasma concentration of ACTH and prostaglandin E2. However, pre‐treatment with systemic administration of indomethacin, an inhibitor of prostaglandin synthesis, significantly suppressed this increase in plasma ACTH. 3. The i.v. injection of prostaglandin E2 significantly increased the plasma concentration of ACTH in a dose‐dependent manner. In contrast, ACTH responses induced by the i.v. injection of prostaglandin E2 were significantly suppressed by systemic pre‐treatment with anti‐corticotrophin‐releasing factor antibody (anti‐CRF), although the plasma level of ACTH still increased in comparison to the basal level. 4. These results suggest that NA‐stimulated prostaglandin release is involved in the ACTH response induced by NA. In addition, it is likely that CRF may be responsible for a portion of the ACTH response induced by i.v. injection of prostaglandin E2.

Spontaneous wheel running attenuates cardiovascular responses to stress in rats

We investigated the effect of chronic, 10-week spontaneous wheel running (SWR) exercise on stress-induced cardiovascular responses in free-moving male rats, using a biotelemetry system. During cage-switch stress or immobilization stress, blood pressure and heart rate were significantly increased in both the SWR (P<0.001 for each stress) and control groups (P<0.001 for each stress). However the blood pressure response was attenuated significantly in the SWR group (P<0.001) during cage-switch stress, and the blood pressure and heart rate responses were attenuated significantly in the SWR group (P<0.0001 and 0.01, respectively) during immobilization stress. The plasma norepinephrine (NE) response induced by immobilization stress tended to be attenuated in the SWR group, but the groups showed no significant differences in the plasma NE and epinephrine (E) responses to both stresses. These results suggest that daily SWR in rats has beneficial effects in suppressing excessive blood pressure and heart rate responses induced by two different types of stress. The mechanisms responsible for the greater resistance to these stresses in the SWR rats should be investigated further.

Effects of running training on the blood glucose and lactate in rats during rest and swimming

The purpose of this study was to examine the effect of physical training on the concentrations of glucose and lactate in the blood of rats during rest and after an acute bout of exercise. We used the following types and periods of training; (i) swimming for 4 weeks, (ii) running for 4 weeks, and (iii) running for 10 weeks. The results clearly show that the resting levels of blood glucose was significantly lower in groups trained by either swimming or running than untrained groups. In addition, after the acute exercise of swimming, animals trained by either running or swimming showed a lower increase in the blood lactate than untrained animals. Furthermore, the increases in the blood glucose after swimming were significantly lower in the group trained by swimming for 4 weeks and by running for 10 weeks than in untrained groups. These results suggest that after physical training by running, animals show an adaptation in the changes in the blood glucose and the blood lactate that are induced by a different type of physical stress, swimming.

Involvement of central β-adrenoceptors in the tachycardia induced by water immersion stress in rats

The purpose of the present study was to investigate whether central beta-adrenoceptors are involved in stress-induced cardiovascular responses in rats. Using a biotelemetry system, blood pressure and heart rate were measured at rest and during stress induced by immersion in 1 cm-deep water. Intracerebroventricular (i.c.v.) injections of a nonselective beta-adrenoceptor antagonist, DL-propranolol (5 or 50 microg), significantly and dose dependently attenuated the tachycardia induced by water immersion stress (drug-induced reduction of tachycardia at 5 min after the start of stress: 61.4 +/- 13.2% for 5 microg, 72.5 +/- 8.2% for 50 microg). The same doses of DL-propranolol had no effect on the resting heart rate. Injection (i.c.v.) of a lower dose (5 microg) of D-propranolol--which has a lower potency as a beta-adrenoceptor antagonist than DL-propranolol, but a similar local anesthetic, membrane-stabilizing activity--did not attenuate the stress-induced tachycardia, although a higher dose (50 microg) did. Intravenous administration of DL-propranolol (5 or 50 microg) significantly attenuated the stress-induced tachycardia (drug-induced reduction of tachycardia at 5 min after the start of stress: 20.0 +/- 7.5% for 5 microg, 42.4 +/- 3.4% for 50 microg). However, the attenuation was much smaller than in the i.c.v. DL-propranolol-injected group. The i.c.v. injection of the 50 microg dose of DL-propranolol significantly augmented both the resting blood pressure and the pressor response to water immersion stress, whereas the lower dose (5 microg) had no effect. The i.c.v. injection of 50 microg D-propranolol also augmented, although not significantly, the resting blood pressure and the pressor response to stress. These results suggest that central beta-adrenoceptors are involved in the tachycardia induced by water immersion stress in rats.