Effect of arginine vasopressin on regional adrenal blood flow and plasma cortisol concentration in fetal sheep.

OBJECTIVE: To determine whether arginine vasopressin (AVP) at plasma concentrations measured during moderate hypoxemia affects adrenal blood flow. STUDY DESIGN: Regional blood flows were measured in 5 unanesthetized normoxemic fetuses (124-128 days' gestation) during a 24-h intravenous infusion of AVP in isotonic saline solution. Another 5 fetuses received an infusion of vehicle. Blood flows were determined before the infusion and at 2 h and 24 h from its onset using radionuclide-labeled microspheres. RESULTS: At 2 h and 24 h of AVP infusion, fetal plasma concentrations of IR-AVP had risen from 4.7 +/- 0.9 pg/ml to 9.8 +/- 1.1 pg/l and 9.4 +/- 0.7 pg/ml, respectively. Thus we achieved plasma concentrations of IR-AVP comparable to those previously reported during moderate hypoxemia. There was no significant effect of treatment on fetal plasma concentrations of immunoreactive adrenocorticotropic hormone (ACTH) or cortisol. AVP infusion significantly decreased fetal heart rate and raised cotyledonary blood flow from 198 +/- 18 ml/min per 100 g to 235 +/- 17 ml/min and 218 +/- 10 ml/min per 100 g at 2 h and 24 h, respectively, from the start of the AVP infusion. Basal values for adrenal medullary and cortical blood flows were similar in the AVP and saline groups, and did not change significantly during the infusions. CONCLUSION: These findings suggest that the rise in adrenal blood flow seen after hypoxemia is not due to a direct action of systemic AVP, but is attributable to other influences, likely including changes in circulating ACTH.

Oral cadmium chloride intoxication in mice: effects of chelation.

In acute oral cadmium intoxication, the immediate target organ is the gastrointestinal tract. In this study, toxic effects following oral administration of CdCl2 to mice by stomach tube included intestinal paralysis, constipation and necrosis of the gastrointestinal epithelia. Tissue damage in liver, kidneys and testes developed in survivors due to the systemic toxicity of absorbed cadmium. Chelation of the Cd2+ ion by STPP, EDTA or DTPA prior to oral administration reduced mortality, tissue damage and whole body retention of cadmium. Other chelators (cysteine, NTA, DDC) only marginally affected the whole-body retention. DDC even enhanced the inhibition of intestinal motility caused by cadmium. DTPA and DDC decreased the relative deposition in the liver and increased the relative renal deposition. DDC also increased the relative cadmium deposition in brain, lung, spleen and testes. Among the chelators tested, DTPA was most efficient in preventing toxic effects of oral cadmium.

Reduced albuminuria during early and aggressive antihypertensive treatment of insulin-dependent diabetic patients with diabetic nephropathy.

Urinary albumin excretion rate (radial immunodiffusion), glomerular filtration rate (GFR) (single-shot 51Cr-EDTA technique), and arterial blood pressure (BP) were measured in 12 juvenile-onset, insulin-dependent diabetic patients with persistent proteinuria (greater than 0.5 g/day) due to diabetic nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0.001), the urinary albumin excretion rate diminished from 1447 to 613 micrograms/min (P less than 0.005), and GFR declined from 96 to 89 ml/in/1.73 m2 (P less than 0.01). A linear relationship between mean blood pressure and the logarithm of the albuminuria was found (r = 0.48, P less than 0.01). Arterial hypertension is an early feature of diabetic nephropathy in young insulin-dependent patients. Early and aggressive treatment of that condition decreases albuminuria, probably due to reduced intraglomerular filtration pressure. Whether sustained reduction in arterial blood pressure to near-normal levels during several years also reduces the rate of decline in GFR in diabetic nephropathy remains to be established.