Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart.

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily of cytokines, possesses hypertrophic actions and atrial natriuretic peptide (ANP)-producing activity in vitro. The goal of our study is to elucidate whether CT-1 affects the cardiovascular system in vivo. Intravenous injection of CT-1 (4-100 microg/kg) in conscious rats evoked significant declines in blood pressure and reflex increases in heart rate (HR) in a dose-dependent manner. CT-1 induced no significant change in cardiac output (from 260.7 +/- 11.0 to 264.7 +/- 26.6 ml. min(-1). kg(-1), P = not significant), which was compatible with the results from isolated perfused rat hearts; HR, change in pressure over time, left ventricular developed pressure, and perfusion pressure were unaffected. Northern blot and RT-PCR analyses revealed that CT-1 increased expression of inducible nitric oxide synthase (iNOS) in lung and aorta but not in heart or liver. Pretreatment with aminoguanidine, a specific iNOS inhibitor, inhibited both iNOS mRNA production and the depressor effect of CT-1. Interestingly, CT-1 increased ventricular expression of ANP and brain natriuretic peptide (BNP). The data demonstrate that CT-1 elicits its hypotensive effect via a nitric oxide-dependent mechanism and that CT-1 induces ANP and BNP mRNA expression in vivo.

The effects of atrial natriuretic peptide infusion on hemodynamic, renal, and hormonal responses during gastrectomy.

UNLABELLED: Atrial natriuretic peptide (ANP) antagonizes the reninangiotensin-aldosterone, adrenocorticotropic hormone-cortisol, vasopressin, and endothelin systems. Surgical injury stimulates these systems and causes vasoconstriction and antidiuresis. We assessed the hemodynamic, renal, and endocrine effects of continuous intravenous infusion of ANP in patients anesthetized with sevoflurane undergoing gastrectomy. ANP (0.1 microgram.kg-1.min-1; ANP group, n = 9) or saline (control group, n = 9) was infused continuously for 3 h from the start of the operation. The ANP group showed much higher urinary volume and sodium, potassium, and chloride excretion than the control group, although the former had lower arterial blood pressure. ANP infusion slightly inhibited aldosterone secretion and initially tended to inhibit renin secretion stimulated by surgery, but it did not affect surgery-induced increases in the plasma concentrations of vasopressin, adrenocorticotropic hormone, cortisol, or endothelin. Two patients in the ANP group experienced excessive hypotension, one experienced bradycardia, and two experienced mild hypoxemia, which required treatment but were resolved easily. These findings suggest that ANP infusion may be used with caution for controlling renal function and arterial blood pressure during surgery. IMPLICATIONS: Continuous intravenous infusion of atrial natriuretic peptide, 0.1 microgram.kg-1.min-1, during gastrectomy was associated with higher water and sodium excretion and lower arterial blood pressure. It tended to inhibit the renin-angiotensin-aldosterone system compared with saline infusion, which suggests that atrial natriuretic peptide may be useful for intraoperative circulation control.

[Are we legally allowed to administer blood for lifesaving to a patient who refuses it?].

We surveyed the literatures and discussed the legal issues whether we should administer blood for lifesaving to a patient who refuses it. The valid refusal of the transfusion requires the distinct intention of a competent patient. Minors below fifteen years of age are incompetent and their parents make a substituted judgement. Anyone must not give priority to the parents' belief and blood ought to be transfused if necessary for the children's benefits. We could evade liability for withholding blood only when we manage an operation arranged to succeed without blood transfusion, undergoing the sufficient treatments to avoid the risks, as well as on the basis of the valid refusal of a patient. The release deed and the intervention of hospital directors, ethics committees and courts are invalid for the immunity from liability. Anesthesiologists have to take the responsibility on themselves of administering blood or not. A statute law should be established to define what is a patient's valid intention and who is responsible.

Immunohistochemical detection of truncated APC protein in sporadic human colorectal adenomas and adenocarcinomas.

Mutations of the APC gene frequently occur in sporadic forms of colorectal adenomas and adenocarcinomas. Phenotypically, the vast majority of these mutations result in the truncation of the APC protein. To demonstrate the defective APC gene product in human colorectal tumors, rabbit region-specific antisera raised against the APC protein of amino acid sequences between 371 and 390 (SPI) and between 1821 and 1840 (SP3) were used to exhibit the truncated APC protein. In all, 86 lesions from 67 cases of sporadic adenoma and adenocarcinoma were examined; abnormal staining patterns were distinguished in 43 lesions (50%); the incidence of abnormalities was not significantly different between adenomas and carcinomas. The majority, 75% exhibited epitopic change with the SPI-positive and SP3-negative phenotype (type P1), and 25% exhibited neither of these phenotypes (type P2). The staining pattern in all lesions was uniform, and studies of carcinomas arising in adenomas showed the same pattern of staining. These findings supported the view that the APC lesion is a very early event in colorectal carcinogenesis. Furthermore, this simple immunohistochemical approach demonstrated that different adenomas from the same patient showed different staining patterns.

Perioperative plasma concentrations of endothelin and natriuretic peptides in children undergoing living-related liver transplantation.

To investigate the clinical significance of endothelin (ET), natriuretic peptides, and the renin-angiotensin-aldosterone system in pediatric liver transplantation, we measured plasma levels of ET, atrial and brain natriuretic peptides (ANP, BNP), aldosterone, and plasma renin activity in 18 patients (aged 0.5-12 yr; median 1 yr) undergoing living-related liver transplantation due to congenital biliary atresia and severe liver cirrhosis. Before transplantation, the plasma ET level (28.9 +/- 2.5 [mean +/- SEM] pg/mL) was increased compared with that of healthy children (10-18 pg/mL), but decreased during the anhepatic phase (22.5 +/- 1.6 pg/mL). It increased again after reperfusion and remained at high levels in the early postoperative period (postoperative day 3, 27.8 +/- 3.0 pg/mL). Plasma levels of ANP and BNP and aldosterone and plasma renin activity were also high before surgery. Plasma ANP and BNP did not change significantly during surgery. After transplantation, plasma BNP significantly increased, and plasma ANP tended to increase. Plasma aldosterone increased markedly during the anhepatic phase, although plasma renin activity decreased. After transplantation, plasma aldosterone and plasma renin activity both decreased to within normal levels. Mean arterial blood pressure increased gradually after reperfusion and surgery (postoperative day 3, 35.7 +/- 5.2% increase). No substantial differences in these variables occurred between the younger (< or = 1.0 yr, n = 9) and older patients (> 1.0 yr, n = 9). These results suggest that ET production in the cirrhotic liver is augmented and ET, natriuretic peptides, and the renin-angiotensin-aldosterone system all play some role in the circulatory regulation during perioperative periods of pediatric liver transplantation.

Effects of anesthesia and surgery on plasma endothelin levels.

To investigate the clinical significance of endothelin (ET), a potent and long-acting vasoconstrictor peptide in anesthesia and surgery, we measured plasma ET-like immunoreactivity (ET-LI) levels by using radioimmunoassay in patients undergoing various kinds of surgery under general anesthesia. No significant changes in plasma ET-LI levels were observed in patients undergoing relatively minor surgery under general anesthesia with nitrous oxide and halothane (n = 6), enflurane (n = 6), or isoflurane (n = 5). Although plasma ET-LI levels after surgery in patients undergoing total knee replacement (12.4 +/- 0.9 [mean +/- SEM] pg/mL, n = 7), hysterectomy (11.4 +/- 0.6 pg/mL, n = 8) or cholecystectomy (14.8 +/- 1.2 pg/mL, n = 9) were no different from those before surgery, plasma ET-LI levels after surgery in patients undergoing gastrectomy (20.4 +/- 1.9 pg/mL, n = 15), esophagectomy (24.7 +/- 2.5 pg/mL, n = 12), hepatectomy (27.5 +/- 3.4 pg/mL, n = 12), or heart surgery (43.1 +/- 4.1 pg/mL, n = 18) were higher than those before surgery (P < 0.05). Changes in plasma ET-LI levels during surgery had positive correlations with the duration of the operation (n = 100, r = 0.51, P < 0.01) and intraoperative blood loss (n = 100, r = 0.30, P < 0.01). In patients undergoing subtotal esophagectomy, the plasma ET-LI level did not increase during the initial 2 h, but increased gradually during surgery, reached a peak within a few hours after surgery, and declined slowly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of endothelin concentration in cerebrospinal fluid and plasma of patients with aneurysmal subarachnoid hemorrhage.

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ET-LI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET-LI levels in plasma and CSF (n = 24) were 12.4 +/- 2.0 (mean +/- s.d.) and 9.1 +/- 1.2 pg.ml-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8 +/- 7.8 pg.ml-1, n = 8) were higher than the normal values (P < 0.05), and became further elevated after surgery (22.5 +/- 9.4 pg.ml-1). ET-LI levels in plasma and CSF one day after surgery were 18.7 +/- 5.5 and 18.4 +/- 6.8 pg.ml-1 (P < 0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.

Positive end-expiratory pressure ventilation decreases plasma atrial and brain natriuretic peptide levels in humans.

To investigate the possible role of atrial and brain natriuretic peptides (ANP and BNP) in the renal effects of mechanical ventilation with positive end-expiratory pressure (PEEP), we measured changes in plasma ANP and BNP levels during PEEP in patients undergoing subtotal esophagectomy. Application of 15 cm of H2O PEEP for 1 h decreased the levels of plasma ANP and BNP from 24.4 +/- 5.5 (mean +/- SEM) and 19.0 +/- 3.5 fmol/mL to 14.4 +/- 2.1 and 15.3 +/- 3.0 fmol/mL, respectively (P < 0.05). The level of plasma cyclic guanosine monophosphate, an intracellular second messenger of ANP and BNP, also decreased from 8.4 +/- 1.5 to 5.7 +/- 0.8 pmol/mL (P < 0.05). PEEP increased the levels of plasma arginine vasopressin from 2.0 +/- 0.5 to 4.2 +/- 1.2 pg/mL, aldosterone from 36.1 +/- 4.9 to 65.3 +/- 12.7 pg/mL, and plasma renin activity from 1.4 +/- 0.5 to 2.7 +/- 0.7 ng.mL-1.h-1. During PEEP ventilation, urine output, urinary sodium and potassium excretion, osmolar clearance, and cardiac index all decreased. PEEP increased free water clearance, right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. The level of plasma endothelin, mean blood pressure, and heart rate did not change significantly. These results suggest that not only hemodynamics and the vasopressin and renin-angiotensin-aldosterone system, but also the natriuretic peptide system (ANP and BNP), are involved in the renal effects of PEEP.

Low doses of endothelin-1 inhibit atrial natriuretic peptide secretion.

To clarify the interaction between endothelin-1 (ET-1) and atrial natriuretic peptide (ANP), the effects of ET-1 on ANP secretion were investigated in isolated perfused rat hearts and in conscious unrestrained rats. Perfusion with 10(-9) M ET-1 stimulated ANP secretion from the isolated perfused rat heart. However, 10(-10) M ET-1 significantly decreased ANP secretion for the initial 15 min of the perfusion period. The perfusion with 10(-11) M ET-1, which is near the plasma level of ET-1 (2 x 10(-12) M), inhibited ANP secretion throughout the perfusion period. The perfusion of 10(-12) M ET-1 slightly decreased ANP secretion. After the ET-1 perfusion period, ANP secretion increased in proportion to ET-1 dose. The inhibitory action of ET-1 on ANP secretion was almost abolished by simultaneous perfusion of indomethacin, a cyclooxygenase inhibitor, but not by methylene blue, an inhibitor of soluble guanylate cyclase. In conscious unrestrained rats the iv infusion of 1 pmol/kg.min ET-1, which doubled the plasma ET-1 level, slightly but significantly decreased the plasma ANP level 5 and 10 min after the initiation of the infusion. The infusion of 10 and 30 pmol/kg.min ET-1 increased the plasma ANP level. These results demonstrate that low doses of ET-1 exert an inhibitory and short-acting action on ANP secretion from the heart, although high doses of ET-1 exert stimulating and long-lasting action, and suggest that prostanoids are involved in this inhibitory action.

Effects of the new anti-ulcer agent 12-sulfodehydroabietic acid monosodium salt on healing of acetic acid-induced gastric ulcers in rats.

The macroscopic and microscopic effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711, CAS 86408-72-2) on the healing of acetic acid-induced gastric ulcers in rats were compared with those of sucralfate and carbenoxolone. Test compounds were given orally twice a day for 10 consecutive days from the day after the injury with glacial acetic acid. TA-2711 (50 and 100 mg/kg) dose-dependently decreased the macroscopic ulcer index (mm2). In addition, at a dose of 100 mg/kg, this drug decreased the length of mucosal defect in the ulcerated region and increased the mucosal regeneration index estimated by microscopic observation. Furthermore, the mucosa surrounding the ulcerated area and the regenerated epithelium in the TA-2711 administered group contained more PAS (periodic acid-Schiff)-positive material than those in the control group. On the other hand, neither sucralfate nor carbenoxolone (100 mg/kg) showed any significant effects on ulcer healing.

Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats.

To investigate the effect of pulmonary alveolar hypoxia on the synthesis and release of endothelin (ET)-1, ET-1-like immunoreactivity (-LI) levels of the lung and plasma were measured in conscious unrestrained rats under hypoxic conditions. Sixty-min exposure to alveolar hypoxia (10% O2 or 5% O2) increased the ET-1-LI level in the lung. The plasma ET-1-LI level in hypoxic rats also increased significantly. The increase of plasma and lung ET-1-LI levels were parallel to the severity of hypoxia. These results demonstrates that acute pulmonary alveolar hypoxia increases lung and plasma ET-1-LI levels in conscious unrestrained rats, suggesting a possible physiological or pathophysiological significance of ET in alveolar hypoxia.

[Granulocyte beta-adrenoceptor density increased with methylprednisolone in patients receiving dopamine infusion].

Methylprednisolone (MP) is frequently used in shock states, its antishock mechanisms, however, have not been clarified. Effect of MP 10 mg.kg-1 on granulocyte beta-adrenoceptor density was studied in two patients who required dopamine infusion postoperatively. The granulocyte beta-adrenoceptor density was calculated from the binding of [3H] dihydroalprenolol. Arterial blood pressure and cardiac output increased 1 hr after MP administrations. Beta-adrenoceptor densities were low in both cases prior to the administration of MP (16.1 and 24.6 fmol.mg-1 protein), which increased 11 hr after MP (31.2 and 35.8 fmol.mg-1 protein, respectively). The effects of MP to improve status of cardiovascular system in patients receiving catecholamine-infusion may be associated with the increase in the density of myocardial "down-regulated" beta-adrenoceptor.

Effects of the new anti-ulcer agent 12-sulfodehydroabietic acid monosodium salt on duodenal alkaline secretion in rats.

Alkaline secretion was measured by pH-stat titration (pH 7.4) during circulation of 0.15 mol/l NaCl through the duodenal lumen in urethane-anesthetized rats. 12-Sulfodehydroabietic acid monosodium salt (TA-2711), at concentrations of 5 and 10 mg/ml, instilled into the circulating fluid at pH 7.4 caused a slight increase in alkaline secretion. When the duodenal lumen was acidified to pH 2.0 for 5 min by instillation of HCl into the circulating fluid, a remarkable increase in alkaline secretion occurred. Addition of TA-2711 (5 and 10 mg/ml) to the circulating fluid considerably enhanced the acid-induced alkaline secretion, with a concurrent increase in prostaglandin E2 release into the circulating fluid. These effects of TA-2711 were inhibited by the pretreatment with indometacin (10 mg/kg s.c.). The results indicate that TA-2711 has an enhancing effect on acid-induced alkaline secretion and endogenous prostaglandins may be involved in the alkaline secretion enhanced by TA-2711.

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric mucosal lesions induced by necrotizing agents and gastric mucosal defensive factors in rats.

Effects of TA-2711 on gastric mucosal lesions induced by various necrotizing agents and several defensive factors of gastric mucosa were investigated in rats. Oral administration of TA-2711 at 12.5 to 200 mg/kg prevented the formation of gastric mucosal lesions induced by 99.5% ethanol, 0.6 N HCl, 0.2 N NaOH and boiling water with ED50 values of 24, 58, 16 and 101 mg/kg, respectively. Oral TA-2711 at 100 mg/kg increased the gastric mucosal prostaglandin E2 (PGE2) level without any change in transmucosal potential difference. A sustained decrease in gastric mucosal blood flow produced by intragastric administration of 99.5% ethanol was inhibited by oral TA-2711 (50, 100 mg/kg) and 16,16-dimethyl PGE2 (10 micrograms/kg). The effect of TA-2711 on ethanol-induced decrease in blood flow was suppressed by indomethacin (10 mg/kg, s.c.). Oral TA-2711 (25-100 mg/kg) dose-dependently increased the amount of mucus adherent to the gastric mucosa. In addition, gastric HCO3- secretion was increased by intragastric TA-2711 at 2.5 and 5.0 mg/ml. These results suggest that TA-2711 enhances gastric mucosal resistance by increasing mucus and HCO3- secretion and by maintaining mucosal blood flow, and protects the gastric mucosa against various irritants. The effects of TA-2711 appear to be mediated by mucosal prostaglandins such as PGE2.

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers in rats.

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers were investigated in rats. Oral administration of TA-2711 at doses of 25 to 100 mg/kg immediately after pyloric ligation markedly reduced pepsin activity and slightly lowered acid concentration without affecting the volume of gastric juice. Addition of TA-2711 (0.25-16 mg/ml) directly to gastric juice also reduced pepsin activity in vitro. Oral TA-2711 dose-relatedly inhibited the formation of pylorus-ligated ulcers (50-200 mg/kg), aspirin-induced gastric erosions (25-100 mg/kg) and cysteamine-induced duodenal ulcers (100-800 mg/kg). In addition, this drug prevented both the formation of gastric lesions (6.3-100 mg/kg, p.o.) and the fall in gastric potential difference (100 mg/kg, p.o.) induced by ethanol. The preventive effect against ethanol-induced lesions was suppressed by pretreatment with indomethacin (10 mg/kg, s.c.). Intravenous dosing of TA-2711 (10-100 mg/kg) never produced such effects on ethanol-induced lesions and pepsin activity as observed by oral administration. These results indicate that TA-2711 exerts its anti-ulcer effect by a local action, and it is suggested that both reduction of pepsin activity and a mucosal prostaglandin-mediated process are involved in the anti-ulcer action of TA-2711.

Possible activation of intracellular beta-adrenoceptors by extraneuronally accumulated isoprenaline in perfused rat heart.

Two rat hearts were perfused in series by a modified Loewi's method. The recipient heart was perfused with the perfusate collected from the donor heart. 1. After perfusion with 3H-isoprenaline in the presence of tropolone, an inhibitor of catechol-O-methyltransferase, the donor heart was washed out with amine-free medium containing tropolone and corticosterone. The heart rate of the recipient heart increased after the change to the perfusate from the donor heart during the wash-out. After wash-out the heart rate of the donor heart (which had accumulated 43.4 pmol.g-1 3H-isoprenaline) was higher than that of the recipient heart (which had accumulated 0.44 pmol.g-1 3H-isoprenaline), and the rates of efflux of 3H-isoprenaline from both hearts were similar. 2. After perfusion with 3H-isoprenaline and corticosterone in the absence of tropolone, the enhanced heart rate of the donor heart decreased during wash-out with amine-free medium in the presence of corticosterone. The heart rate of the recipient heart increased after the medium change to the perfusate from the donor heart, and the heart rates in both hearts were similar after wash-out. Only small amounts of 3H-isoprenaline remained in both hearts after wash-out, and the rates of efflux of 3H-isoprenaline from both hearts were similar. 3. After perfusion with 3H-isoprenaline in the presence of tropolone, the effects of propranolol and atenolol on the heart rate during wash-out with amine-free medium containing tropolone and corticosterone were compared. The inhibitory effect of propranolol on the heart rate was significantly greater than that of atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart.

Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart was investigated. Rat hearts were perfused with various concentrations of 3H-isoproterenol for 30 min in the absence and the presence of catechol-O-methyltransferase (COMT) inhibitor (tropolone). When COMT was intact, the accumulation of 3H-isoproterenol in both atria and ventricle after perfusion with low concentration of 3H-isoproterenol (0.01 to 1 mumol/l) was less than that of perfusing concentration; the tissue/medium ratio (T/M) of isoproterenol for artia was lower than that for ventricle. The T/M of isoproterenol after perfusion with 10 and 20 mumol/l of 3H-isoproterenol were 0.94 and 1.76 for atria and 3.25 and 2.95 for ventricle, respectively. When COMT was inhibited by tropolone, the T/M increased 6.3-9.0 folds for atria and 5.1-6.7 folds for ventricle after perfusion with 3H-isoproterenol (0.01 to 1 mumol/l). From these results, it was concluded that both atria and ventricle of the rat heart have an extraneuronal O-methylating system as reported in rat whole heart, and was suggested that there might be different capacities of extraneuronal uptake and COMT between them.

Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. V. Comparative studies of the biological properties.

Chloropolysporins A, B and C, as well as derivatives prepared from this group and alpha- and beta-avoparcins by enzymatic and mild acid hydrolysis, were active against Gram-positive bacteria including clinically isolated methicillin-resistant Staphylococci (MIC 0.39-6.25 micrograms/ml) and anaerobic enterobacteria (MIC 0.10-1.56 micrograms/ml). Derhamnosyl and demannosyl derivatives from both groups of antibiotics showed stronger activities than the parent compounds. The MIC and MBC values against Staphylococci were similar and were not effected by the presence of serum. Moreover, chloropolysporin C exhibited very strong synergistic effects with various beta-lactam antibiotics against methicillin-resistant strains of Staphylococcus aureus. Some of these compounds also protected mice from experimental infection with S. aureus. Acute toxicities of chloropolysporin by intravenous administration ranged from 215-290 mg/kg in mice. Chloropolysporin B as well as other glycopeptide antibiotics, showed distinctive growth promoting activity in broiler chickens.

Differential effects of hypoxia on the turnover of norepinephrine and epinephrine in the heart, adrenal gland, submaxillary gland and stomach.

The authors examined the effects of hypoxia (8% O2 in N2) on the turnover rates of norepinephrine (NE) and epinephrine (E) in the heart, adrenal gland, submaxillary gland and stomach. The turnover rates were estimated by measuring the decrease in the content of NE and E after an i.p. injection of alpha-methyl-p-tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. After a 4-h exposure to hypoxia, the turnover rate of NE in the heart and those of NE and E in the adrenal gland were increased, whereas that of NE in the submaxillary gland was decreased. The turnover rate of NE in the stomach was unchanged. Pretreatment with hexamethonium, a ganglionic nicotinic receptor blocker, abolished the hypoxia-induced changes in the turnover rate of NE or E in the heart, adrenal gland and submaxillary gland. Furthermore, transection of the spinal cord at the level of C5-6 abolished hypoxia-induced alterations in the turnover rate of NE and E in the adrenal gland and submaxillary gland. In contrast, the hypoxia-induced changes seen in the heart persisted, although at a lower level, even after transection. These results show that the effects of hypoxia on the activities of the sympathoadrenal system differ depending on the organs; activities are increased in the heart and adrenal gland, decreased in the submaxillary gland and unchanged in the stomach. Furthermore, the present data suggest that hypoxia-induced alterations in the activities of cardiac sympathetic nerves originate in both the brain and spinal cord, including preganglionic neurons, whereas changes in the activities of the sympathetic nerves to the adrenal gland and submaxillary gland originate mainly in the brain.