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Background: Pain in glossodynia may be severe; it may prevent patients from working, interfere with daily life activities, and necessitate a patient's visit to a medical institution for consultation and treatment. The pain may be described as persistent and burning (tingling, tingling) or stinging. Patients may complain of dry mouth (dryness), which is thought to cause inflammation of the tongue and gingival mucous membranes and increased pain. Medications are prescribed based on the symptoms of glossodynia, and the therapeutic effect is confirmed. However, each drug has side effects, for example, pain may reduce, but drowsiness and dizziness may occur; further, there is always a tendency of drowsiness.On the other hand, Goreisan, a Chinese herbal medicine, has already been used by physicians to treat pain in the oral and maxillofacial regions resulting from rapid changes in air pressure. However, the lack of high-quality clinical research has been of concern, and a randomized clinical trial to investigate the efficacy and safety of Goreisan for treatment of pain in glossodynia is warranted., Methods/design: This multicenter, randomized, controlled study will involve patients treated for glossodynia-related pain. In the experimental group, Goreisan will be taken for 12 weeks in combination with conventional treatment. Participants in the control group will not take any Kampo medicine; only the standard treatment will be taken. Subsequently, the degree of pain will be assessed, and saliva tests of all the patients on their first visit will be performed. Goreisan will be taken at a dose of 7.5 g/d (minute 3) for 12 consecutive weeks. Twelve weeks later, the degree of pain of each patient will be assessed., Discussion: The purpose of this study is to investigate the efficacy of Goreisan for pain reduction in patients undergoing treatment for glossodynia-related pain. If pain in glossodynia patients can be reduced by the administration of Goreisan, its candidacy as an alternative treatment for pain in glossodynia can be further supported by more reliable research., Trial Registration: The study was registered in the jRCTs071200017. URL https://jrct.niph.go.jp/latest-detail/jRCTs071200017.

Background: Current cardioplegic protection techniques used in pediatric cardiac surgery do not take into consideration age and cyanotic differences. The aim of the present work was to address this question by monitoring clinical outcome, myocardial metabolism, and reperfusion injury in pediatric patients protected by cold-crystalloid cardioplegia., Methods and Results: Fifty-eight patients (31 children and 27 infants) with or without hypoxic stress (cyanosis) undergoing open heart surgery with cold-crystalloid cardioplegia were included in the study. Clinical outcome measures assessed included inotropic and ventilatory support, intensive care, and hospital stay. Ischemia-induced changes in metabolism (adenine nucleotides, purines, lactate, and amino acids) were determined in ventricular biopsies collected at the beginning and end of ischemic time (cross-clamp time). Reperfusion injury was assessed by measuring postoperative serial release of troponin I. Evidence was observed of ischemic stress during cardioplegic arrest in children and infants as shown by significant changes in cellular metabolites. Compared with infants, children had significantly less reperfusion injury and better clinical outcome, and these factors were related to duration of ischemic time. Cyanosis did not influence outcome in infants, but cyanotic children showed worse reperfusion injury and clinical outcome than acyanotic children., Conclusions: Extent of myocardial protection with cold-crystalloid cardioplegia in pediatric open heart surgery is dependent on age and degree of cyanosis.

Background: Brain natriuretic peptide (BNP), as a cardiac hormone, is expressed together with atrial natriuretic peptide (ANP) in the ventricles in congestive heart failure. However, the ventricular expression of BNP in hypertrophic cardiomyopathy (HCM) with normal systolic function is still unclear., Methods and Results: The study population consisted of 39 HCM patients with asymmetric septal hypertrophy and 10 control subjects without any specific cardiac disease. Eleven cases of HCM were obstructive (HOCM), and the other 28 cases were nonobstructive (HNCM). All of these patients had a normal ejection fraction. Immunohistochemical analysis of endomyocardial biopsy specimens with specific monoclonal antibodies showed BNP immunoreactivity in the HOCM group (5/10, 50%) but not in the HNCM group (0/22) or in control subjects (0/5). In HOCM, left ventricular end-diastolic pressure was significantly higher in the BNP-positive patients than the BNP-negative patients. Histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis were greater in BNP-positive patients than BNP-negative patients in HCM. However, the expression had no significant relation with other clinical parameters. The elevation of the BNP plasma level versus control subjects was marked in both HOCM (85-fold) and HNCM (23-fold). By contrast, the elevation of the ANP plasma level versus control subjects was mild in HOCM (5.7-fold) and HNCM (4.2-fold). The ratio of BNP level to ANP level was higher in HOCM (4.16) than in HNCM (1.46) and control subjects (0.28), and it was higher than the ratio previously reported for severe congestive heart failure (1.72)., Conclusions: These findings suggest that BNP is expressed in the ventricular myocytes of HCM with normal systolic function. In HOCM, ventricular expression of BNP may be augmented in response to both obstruction and diastolic dysfunction.

Objective: To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension., Methods: We determined the plasma levels of brain and atrial natriuretic peptides in a cross-sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension., Results: During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P < .05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P < .001)., Conclusion: The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation.

Background: The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles., Methods and Results: We measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher in the DCM group than in the MS group (16.4 +/- 7.8 mm Hg versus 7.6 +/- 2.0 mm Hg, p < 0.01), and the level was comparable between the MS and control groups (7.6 +/- 2.0 mm Hg versus 6.8 +/- 1.2 mm Hg, p = NS). The plasma ANP level was significantly higher in the MS and DCM groups (356 +/- 169 pg/ml and 331 +/- 323 pg/ml, respectively) than in the control group (98 +/- 41 pg/ml, p < 0.01), whereas there was no significant difference between the MS and DCM groups. The plasma BNP level was significantly higher in the DCM group than in the MS group (333 +/- 405 pg/ml versus 147 +/- 54 pg/ml, p < 0.01), and the level was significantly higher in the MS group than in the control group (147 +/- 54 pg/ml versus < 10 pg/ml, p < 0.01). The plasma levels of ANP and BNP had a highly positive correlation with PCWP in the DCM group (p < 0.01). On the other hand, in the MS group, the plasma ANP level had a highly significant correlation with PCWP (p < 0.01) but the plasma BNP level did not., Conclusions: We conclude that plasma levels of BNP mainly reflect the degree of ventricular overload and that the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.

The natriuretic peptide system is a complicated system comprising at least three endogenous peptides, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide and three receptors, the atrial natriuretic peptide-A receptor (guanylyl cyclase A), the atrial natriuretic peptide-B receptor (guanylyl cyclase B), and the clearance receptor. The accumulated evidence indicates that this system is implicated in the control of blood pressure, body fluid homeostasis, and vascular remodeling as both cardiac hormone and local regulator.

Oxidatively modified low density lipoprotein (oxidized LDL), an atherogenic lipoprotein that exists in the atherosclerotic arteries, has been shown to alter endothelial cell functions. In the present study, we examined the effects of oxidized LDL on the production of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells from porcine aorta and human umbilical vein. Incubation with oxidized LDL resulted in a dose-dependent suppression of ET-1-LI release by both endothelial cells. Oxidized LDL also inhibited thrombin-mediated stimulation of ET-1-LI secretion. However, native LDL had no effects on ET-1-LI secretion. A lipid extract from oxidized LDL, but not from native LDL, inhibited ET-1-LI secretion, indicating that the lipid component of oxidized LDL was required for the inhibition of ET-1-LI secretion. Oxidative modification of LDL was associated with degradation of a substantial amount of phosphatidylcholine to lysophosphatidylcholine (LPC). Pretreatment with defatted albumin, which is an acceptor for hydrophilic lipids including LPC, reduced LPC concentration in oxidized LDL to that in native LDL and simultaneously prevented the inhibitory effects of oxidized LDL on ET-1-LI secretion. Incubation with synthetic LPC (palmitoyl), but not with synthetic phosphatidylcholine (dipalmitoyl), suppressed ET-1-LI secretion by the endothelial cells. No cell death was observed during the incubations as judged by the trypan blue exclusion test, and protein synthesis of the endothelial cells was not affected by lipids or lipoproteins at a concentration at which suppression of ET-1-LI was observed. We concluded that LPC in oxidized LDL causes suppression of ET-1-LI release, which may counteract the vasoconstrictive properties of atherosclerotic arteries.

Background: To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years)., Methods and Results: Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure., Conclusions: Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.

Background: This study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects., Methods and Results: We infused synthetic human BNP at a rate of 0.1 micrograms/kg/min. BNP infusion decreased pulmonary capillary wedge pressure (control, from 5 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01; CHF, from 21 +/- 3 to 14 +/- 4 mm Hg, p less than 0.05) and systemic vascular resistance (control, from 1,264 +/- 75 to 934 +/- 52 dyne.sec.cm-5; CHF, from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5; p less than 0.01, respectively) and increased stroke volume index (control, from 49.9 +/- 2.7 to 51.5 +/- 2.3 ml/m2, p = NS; CHF, from 25.6 +/- 3.8 to 32.0 +/- 3.9 ml/m2, p less than 0.01). BNP infusion significantly increased urine volume (control, from 2.3 +/- 0.7 to 7.5 +/- 1.9 ml/min; CHF, from 0.8 +/- 0.2 to 5.3 +/- 1.0 ml/min; p less than 0.01, respectively), excretion of sodium (control, from 79.2 +/- 21.6 to 332.8 +/- 70.9 microEq/min; CHF, from 77.4 +/- 20.8 to 753.5 +/- 108.0 microEq/min; p less than 0.01, respectively), and excretion of chloride (control, from 72.5 +/- 18.4 to 256.0 +/- 43.3 microEq/min; CHF, from 74.0 +/- 19.6 to 708.8 +/- 103.3 microEq/min; p less than 0.01, respectively). Urinary excretion of sodium and of chloride in response to BNP infusion was higher in patients with CHF than in control subjects (p less than 0.01, respectively). BNP infusion increased the levels of plasma atrial natriuretic peptide (control, from 65 +/- 11 to 84 +/- 14 pg/ml; CHF, from 262 +/- 65 to 301 +/- 62 pg/ml; p less than 0.05, respectively) and decreased plasma aldosterone concentrations in both groups (control, from 43.3 +/- 12.1 to 27.3 +/- 7.1 pg/ml; CHF, from 91.1 +/- 34.3 to 66.3 +/- 27.2 pg/ml; p less than 0.05, respectively)., Conclusions: We conclude that BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action.

Background: Although first isolated from the porcine brain, brain natriuretic peptide (BNP) is also found in the heart, particularly in the atria., Methods and Results: We examined the immunocytochemical localization of BNP in relation to atrial natriuretic peptide (ANP) in five porcine atria using highly specific monoclonal antibodies. With the use of an indirect immunoperoxidase method, serial sections examined by light microscopy showed foci of multihormonal myocytes containing both ANP and BNP localized in the subendocardium. Monohormonal myocytes containing ANP only were observed in the subepicardium and part of the subendocardium. The staining intensity of ANP and BNP showed a transmural gradient from the subendocardium to the subepicardium. At the electron microscopic level, double immunocytochemistry using a two-face immunogold-staining method revealed two types of granules: Type 1 is a monohormonal granule containing ANP alone, and type 2 is a multihormonal granule containing both ANP and BNP. Although most atrial myocytes contained both, type 1 granules were frequently observed in the epicardial side, and type 2 granules were frequently observed in the endocardial side. We observed a few type 2 granules even in the light microscopically monohormonal myocytes., Conclusions: These data suggest that the atrial myocyte population comprises single, multipotential cells able to synthesize both natriuretic peptides in varying proportions. The atrial transmural gradient of BNP and ANP may be related to responses to wall stress.

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle greater than right ventricle greater than right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.

We measured plasma endothelin-1-like immunoreactivity (ET-1-LI) levels in the peripheral vein of 70 healthy children (37 males and 33 females) aged 5 days to 15 years to establish the normal range in children, and compared them with those in 11 normal adults (age, mean +/- SD; 29.5 +/- 5.7 years, 6 males and 5 females). Plasma ET-1-LI levels (pg/ml, mean +/- SD) in children of each age group and adults were as follows: children younger than 1 month = 23.4 +/- 3.9 (n = 10), 1-3 months = 25.0 +/- 6.1 (n = 8), 3-6 months = 17.0 +/- 1.4 (n = 8), 6 months to 1 year = 14.0 +/- 1.7 (n = 13), 1-5 years = 13.8 +/- 2.6 (n = 11), 5-10 years = 13.6 +/- 1.6 (n = 10), 10-15 years = 12.9 +/- 2.2 (n = 10), and adults = 13.2 +/- 2.4 (n = 11). There was no significant difference in plasma ET-1-LI levels between males and females in each age group. Plasma ET-1-LI levels in children younger than 3 months were significantly (p less than 0.01) higher than those in older children or adults. After 3 months of age, plasma ET-1-LI levels were nearly constant at all ages. This is the first report to establish the normal range of plasma ET-1-LI levels in children.

To investigate the pathophysiological significance of endothelin-1 (ET-1) in renal failure, we measured plasma and urine concentrations of ET-1-like immunoreactivity (LI) by radioimmunoassay (RIA). The plasma ET-1-LI level was significantly increased in hemodialyzed and nonhemodialyzed patients with chronic renal failure (CRF). The increase in the plasma ET-1-LI level in CRF was much larger than that in other diseases in which the plasma ET-1-LI level was reported to be increased. The urine ET-1-LI level was lower, and daily excreted amounts of ET-1-LI were smaller in CRF patients than in normal subjects. These findings indicate that the increased plasma level of ET-1-LI in CRF results from the decreased clearance rate of ET-1-LI in the kidney. Gel permeation chromatographic analysis revealed that ET-1-LI in plasma from CRF consisted of small and large molecular forms of ET-1-LI. The small molecular form is presumably ET-1, and large molecular forms are big ET-1 and another component with the molecular weight of 6,000 as is the case of that in normal plasma (1). However, the ratio of the smaller to large molecular forms of ET-1-LI in CRF was 1:13 and was quite different from that in normal plasma (1:4). These observations clearly indicate that the elevation of plasma ET-1-LI level in CRF was mainly due to the increase in the large molecular form of ET-1-LI.

To clarify whether or not tachycardia stimulates the secretion of atrial natriuretic polypeptide (ANP) without elevation of atrial pressure, we examined the effects of atrial pacing on ANP secretion in awake dogs with normal sinus rhythm and with complete atrioventricular block (CAVB), which was produced surgically by heat cauterization of His' bundle. In four dogs with normal sinus rhythm, atrial pacing increased the atrial rate from 146 +/- 20 to 260 +/- 10 beats/min, with marked elevation of right atrial pressure (from 0.2 +/- 0.1 to 3.9 +/- 0.8 mm Hg) and left atrial pressure (from 0.2 +/- 0.1 to 8.6 +/- 2.8 mm Hg). Along with the hemodynamic changes, the ANP level in plasma obtained from the coronary sinus was increased from 405 +/- 99 to 849 +/- 199 pg/ml (p less than 0.01). In five dogs with CAVB, the ANP level was also significantly increased from 730 +/- 82 to 1,137 +/- 35 pg/ml (p less than 0.01) by rapid atrial pacing (from 164 +/- 20 to 317 +/- 30 beats/min) in spite of the lack of any appreciable changes in either left or right atrial pressure. Furthermore, in the CAVB group, while the ventricular rate was increased by ventricular pacing from 52 +/- 5 to 146 +/- 16 beats/min, atrial pacing was performed simultaneously without atrioventricular (A-V) sequential form. Even under this condition, the ANP level was increased from 480 +/- 172 to 626 +/- 223 pg/ml (p less than 0.05) without any substantial changes in atrial pressure. Such effects of rapid atrial pacing on ANP secretion were suppressed after infusion of autonomic blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of plasma immunoreactive atrial natriuretic polypeptide (IR-ANP) to isotonic volume expansion (100 ml/kg per h for 60 min) were investigated in conscious, unrestrained, chronically guanethidine-treated Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Plasma IR-ANP increased during volume expansion and stabilized with continued infusion of isotonic solution. Guanethidine treatment did not alter resting and maximum responses of plasma IR-ANP. Spontaneously hypertensive rats and WKY showed similar plasma IR-ANP levels before volume expansion. Spontaneously hypertensive rats, however, exhibited earlier rises in plasma IR-ANP and larger increases in blood pressure, while maximum plasma IR-ANP response and total fluid retention (as judged from the weight gain) during volume expansion were similar in both groups. The present study suggests that: ANP release is regulated by the extent of filling of the circulation, sympathetic nervous system does not modulate release of ANP, and SHR have altered responses of ANP to volume overload, which may represent a compensatory mechanism that enables the SHR to eliminate excess sodium and fluid out of the circulation and thereby blunt further increases in blood pressure. In separate studies, we found that ether anaesthesia increases, while pentobarbital decreases the levels of plasma IR-ANP.

Synthetic alpha-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0.1 microgram/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldosterone concentrations in these patients, although no significant difference was observed in the decrement of the plasma aldosterone concentration in the patients with and those without CHF. These findings indicate that the ANP infusion improves left ventricular function in patients with CHF, and suggest that this improvement results mainly from the vasodilating activity of ANP.

To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in diseased hearts, ANP levels in atrial and ventricular tissues and plasma were investigated in mice with congestive heart failure after viral myocarditis. The study was performed on day 14 after encephalomyocarditis viral inoculation, when congestive heart failure developed. The atrial ANP level increased to a value two times higher than that of noninoculated age-matched mice (the control mice). The ventricles of the control mice contained an approximately 1,000-fold lower ANP level than the atrial ANP level. The ventricular ANP concentration of the infected mice showed about a 21 times higher level than the control value. The plasma ANP level was also elevated 20 times. On immunofluorescence studies, increase of immunostaining were found in the atrial of the infected mice, and positive staining appeared on the cardiocytes in almost all areas of the remaining ventricular tissues of the infected mice, whereas staining was not found on the ventricles of the control mice. The staining seemed particularly strong in the area surrounding the myocardial lesions. These results indicate that atrial and ventricular ANP synthesis and ANP secretion increase in the heart with viral myocarditis. The marked increase in the ventricular ANP level suggests that the ventricle is another important production site for circulating ANP.

The origin of the hyperintense signal (HIS) of the pituitary gland posterior lobe (PL) on T1-weighted magnetic resonance (MR) images was investigated. Six rabbits were imaged on a 1.5 T device before and after 2 weeks' feeding of hypertonic saline solution (phase I). Two were killed soon after the second imaging; the pituitary gland was examined histochemically for neurosecretory granules containing antidiuretic hormone (ADH). The other four rabbits were given regular water for another 2 weeks (phase II) and then were again imaged. The plasma ADH level was monitored at each imaging session. In all subjects, the signal intensity of the PL decreased at the end of phase I, and the HIS reappeared at the end of phase II. The neurosecretory granules in the PL significantly diminished in number in phase I. Plasma ADH levels significantly increased in phase I and returned to their normal range in phase II. These clear correlations between MR findings and hormonal and histochemical results strongly suggest that the source of the HIS of the PL is the neurosecretory granules containing ADH.