Kyuzi Kamoi

Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction.

Syndrome of inappropriate antidiuresis without involving inappropriate secretion of vasopressin in an elderly woman: Effect of intravenous administration of the nonpeptide vasopressin V2 receptor antagonist OPC-31260

We describe a 78-year-old female patient with severe hyponatremia owing to inappropriate antidiuresis. Despite hyponatremia, the urinary sodium excretion persisted with urine osmolality exceeding plasma osmolality. Although a water load decreased plasma sodium concentration and osmolality, the patient excreted only 40% of the water load after 4 h without decreased urine sodium concentrations and osmolality. The plasma vasopressin levels relative to plasma osmolality were not inappropriately elevated. Intravenous administration of the selective nonpeptide vasopressin V2 antagonist OPC-31260 decreased sodium concentration and osmolality in urine to lower values than in plasma. Concomitantly, the urine volume excretion increased markedly. In addition, restriction of water or administration of demeclocycline improved plasma sodium and plasma vasopressin levels relative to plasma osmolality to be normal. The findings indicate that the inappropriate antidiuresis in this patient was related to hyperfunction of the arginine vasopressin V2 receptor in the kidney which is not due to inappropriately secreted vasopressin.

Plasma endothelin-1 levels in patients with hyponatremia.

K. Kamoi, MD, Department of Medicine, Nagaoka Red Cross Hospital, Nagaoka, Niigata 940 (Japan) Dear Sir, Endothelin is a potent vasoconstrictor peptide isolated from the culture medium of vascular endothelial cells (1). Recent studies show that endothelin decreases sodium excretion directly or indirectly by changes in renal hemodinamics [2-3]. If endothelin plays a role in the sodium and water homeostasis, then its production and secretion may be altered in various pathologic states associated with hyponatremia. To prove this hypothesis, we measured plasma levels of endothelin-1, the major molecular form of endothelin pep-tides present in human plasma [4], in patients with hyponatremia of different causes. We studied 6 men with the syndrome of inappropriate antidiuretic hormone secretion (SIADH), aged 53-72 years. The diagnosis was established by the criteria of Schwartz et al. [5]. All patients had hyponatremia (mean ± SD: 119 ± 6 mmol/l) and plasma hypoosmolality (241 ± 11 mmol/kg), despite hypertonic urine (431 ± 5 mmol/kg) and sustained urinary sodium excretion (102 ± 28 mmol/l). Their underlying diseases were head injuries in 3, lung cancer in 2, and gastric cancer in 1 patient. We studied also 6 men (aged 64-73 years) with depletional hyponatremia, which resulted from excessive use of diuretics or mannitol infusion in 3 patients with isolated ACTH deficiency, in 2 with head injuries and in 1 with liver cirrhosis. They had hyponatremia (mean ± SD: 121 ± 6 mmol/l) and plasma hypoosmolality (249 ± 18 mmol/kg) and excreted hypertonic urine (564 ± 198 mmol/kg) with urinary sodium loss (107 ± 90 mmol/Γ). The patients were dehydrated and their plasma creatinine -p < O.011.5 -p < O.01 ι.o• 1 : 0.51 1 ! Patients Patients Normalwith SIADH with subjects depletional hyportatremia Fig. 1. Plasma endothelin-1 levels in patients with SIADH, in patients with depletional hyponatremia and in age-matched normal men. Bars represent mean ± SD.