The plasma concentration of arginine vasopressin (AVP) is closely regulated by plasma osmolality. In this study, we used intronic in-situ hybridization to investigate the transcriptional activity of the AVP gene in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) after intraperitoneal (i.p.) injection of hypertonic saline inducing small changes in plasma osmolality in rats. After ip injection of 900 mOsm/kg saline (2% BW), plasma [Na] reached the highest level at 10 min (900 mOsm/kg, 146+/-1 mEq/l; 290 mOsm/kg, 139+/-1 mEq/l, P<0.01) and maintained that level until 30 min. The expression of AVP heteronuclear (hn) RNA in the SON and PVN increased significantly as early as 10 min and peaked 30 min after ip injection of the hypertonic saline. AVP hnRNA expression showed a significant increase even after a 2 mEq/L elevation in plasma [Na] concentration, and increased dose-dependently in response to the concentration of saline injection (290-900 mOsm/kg). These results demonstrate that, similar to AVP secretion, AVP gene transcriptional activity in the SON and PVN is closely regulated by plasma osmolality.

Arginine vAsopressin (Avp) is an antidiuretic hormone which is synthesized in the supraoptic and paraventricular nuclei in the hypothalamus, and released into the systemic circulation from the posterior pituitary [1,2]. Secretion of AVP is precisely controlled by plasma osmolality so that even as little as 1% increases in plasma osmolality or serum sodium levels significantly increase plasma AVP levels [1,2]. Increases in plasma osmolality are sensed via the osmoreceptors in the hypothalamus, and induce not Abstract. Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death.

We investigated the baroregulation of arginine vasopressin (AVP) gene transcription in the supraoptic (SON) and paraventricular nuclei (PVN) in conscious rats by use of intronic in situ hybridization. Hemorrhage of 16 ml/kg body wt decreased mean arterial pressure (MAP) by 57% and increased both plasma AVP (control, 1.2 +/- 0.3 pg/ml; 16 ml/kg body wt, 38.9 +/- 3.2 pg/ml) at 10 min and AVP heteronuclear (hn)RNA levels (SON, 150%; PVN, 140% of control values) at 20 min. On the other hand, hemorrhage of 7 ml/kg body wt had no significant effect on MAP, plasma AVP, or the AVP hnRNA levels. To better understand the baroregulation, we also examined the effects of sodium nitroprusside (SNP), which induces hypotension without a change in blood volume. The subcutaneous injection of 2 mg/kg body wt SNP, which decreased the MAP by 60%, increased both plasma AVP (control, 1.6 +/- 0.4 pg/ml; 2 mg/kg body wt, 8.1 +/- 0.4 pg/ml) at 10 min and AVP hnRNA levels (SON, 150%; PVN, 140% of control values) at 30 min. The injection of 0.1 mg/kg body wt SNP, which reduced the MAP by 10%, failed to increase either the plasma AVP or AVP hnRNA levels. These results indicate that AVP gene transcription increases rapidly after both hypotensive hemorrhage and normovolemic hypotension. In addition, it is suggested that the set point for AVP synthesis in the baroregulation is similar to that for AVP release.

Objective β-adrenergic antagonists (β-blockers) are often used to attenuate the hyperadrenergic symptoms of Graves' disease (GD), including palpitation. Although β-blockers reduce the heart rate, cardiac output and oxygen consumption, no firm evidence exists regarding the effects of combined therapy with β-blockers and anti-thyroid drugs. The objective is to elucidate the effects of β-blockers on anti-thyroid drug therapy in GD. Methods Patients newly diagnosed with mild GD were randomly assigned to receive methimazole with or without β-blockers in a prospective multi-center survey. The heart rate and thyroid function were measured and the quality of life was assessed using original and SF-36 questionnaires at 0 and 4 weeks. Results A total of 28 patients were enrolled in the study. Fourteen patients (one man, 13 women) were randomly assigned to the group treated with β-blockers and 14 patients (one man, 13 women) were randomly assigned to the group not treated with β-blockers. Although no significant differences in the improvement of thyroid function were observed between the two groups, the heart rates improved more significantly in the group treated with β-blockers. Specific symptoms, such as easy fatigability and shortness of breath, also improved more significantly with the β-blocker treatment. In addition, 'physical functioning' assessed with the SF-36 questionnaires significantly improved only in the group treated with β-blockers. Conclusion Although β-blockers may not reinforce the effects of anti-thyroid drugs on thyroid function, at least during the course of one month, they are effective in reducing heart rates and ameliorating specific symptoms in patients with mild GD.