Neurohypophyseal secretion in hypovolemic rats: inverse relation to sodium appetite.

Subcutaneous injection of polyethylene glycol (PEG) solution in rats produces exponential increases in secretion of arginine vasopressin (AVP) and oxytocin (OT) in proportion to the induced plasma volume deficits. Previously, we reported that acute water loads eliminated the neurohypophyseal hormone responses to hypovolemia, whereas hypertonic NaCl potentiated them. The present experiments indicated that AVP and OT secretion after PEG treatment were blunted by prior maintenance of rats on a sodium-deficient diet for 2 days. In contrast, plasma AVP and OT levels after PEG treatment were enhanced by prior adrenalectomy or ligation of the inferior vena cava or by concurrent administration of phentolamine in association with arterial hypotension. AVP and OT responses to hypovolemia were similarly potentiated in rats made uremic by bilateral nephrectomy or by puncturing their bladders. These results parallel previous findings that osmotic dilution and sodium deprivation each enhance the sodium appetite induced by PEG treatment in rats, whereas hyperosmolality, hypotension, and uremia each abolish it. Consequently, they support our previous hypothesis that sodium appetite is inversely related to the activity of hypothalamic oxytocinergic neurons.

Coagulopathy associated with extended-spectrum cephalosporins in patients with serious infections.

Patients enrolled in two double-blind multicenter studies were evaluated for the development of hypoprothrombinemia during treatment with cephalosporins. Patients with pneumonia or peritonitis received ceftizoxime, cefotaxime, or moxalactam. The incidence of hypoprothrombinemia was greater in patients with peritonitis (12 of 49) than in those with pneumonia (5 of 96; P less than 0.05). Overall, moxalactam was associated with a higher incidence of hypoprothrombinemia (13 of 52) than either ceftizoxime (1 of 43; P less than 0.05) or cefotaxime (3 of 50; P less than 0.05), and moxalactam patients incurred the highest average increase in prothrombin time (3.7 s) as compared with either ceftizoxime (0.5 s; P less than 0.05) or cefotaxime (0.9 s; P less than 0.05) patients. The occurrence of hypoprothrombinemia in moxalactam patients with peritonitis was not related to dosage, duration of therapy, age, sex, race, or renal or hepatic function. The degree of ileus was, however, strongly related to the development of coagulopathy in moxalactam-treated patients only.

Effect of antihypertensive treatment on the behavioral consequences of elevated blood pressure.

It was shown in a prior study that mildly hypertensive patients performed significantly less effectively on several sensory-perceptual, cognitive, and psychomotor tests than did matched normotensive controls. To determine whether these deficits are attributable to elevated blood pressure per se, hypertensive and control subjects were recalled for reexamination 15 months after the original tests. Results indicated that those hypertensives in whom blood pressure had been lowered with antihypertensive drugs showed significant restoration of performance scores toward the levels of normotensive subjects. Hypertensives who had not received active treatment remained deficient as compared with controls. These results indicated that behavioral deficits in mild hypertension may be reversible consequences of the effects of elevated blood pressure on the central nervous system.

Impaired drinking responses of rats with lesions on the subfornical organ.

electrolytic lesions of the subfornical organ (SFO) in rats are known to abolish their drinking response to intravenous infusion of angiotensin II (AII). Such lesions also attenuate drinking after 20% polyethylene glycol solution (PEG) is given subcutaneously, which suggests that AII may play an important role in mediating thirst during hypovolemia. However, the present studies show that such rats with SFO lesions may drink normal amounts when larger plasma volume deficits are caused by 30% PEG treatment. They also may drink normal amounts in response to 20% PEG when pretreated either with caffeine or hypertonic NaCl solution. Furthermore, they may not drink in response to relatively low doses of hypertonic saline but drink normal amounts when given larger doses. These and other results suggest that the SFO is involved in a control system for thirst and that after damage to it, greater stimulation than usual may be required for drinking to be initiated. From this perspective, drinking would be expected following either suprathreshold stimulation or drug-induced lowering of the activation threshold in these animals, as was observed, with the loss of putative AII receptors in the SFO also contributing to their particularly severe deficits in thirst induced by AII.