The hemodynamic effect of dietary calcium supplementation on rat renovascular hypertension.

Mechanisms which could be responsible for the hypotensive effects of increasing calcium intake from 1.2 to 2.5% of diet were examined in two kidney, one clip renovascular hypertension (2K, 1C RHV) in male Sprague-Dawley rats. Plasma renin activity was elevated similarly in NCA and HCA rats. No evidence for volume or phosphate depletion was found in HCA animals. Cardiac output was not different. Decreased sensitivity was demonstrated to moderate doses of norepinephrine in HCA rats, while vascular reactivity to exogenously administered angiotensin II over the range of doses used was not different between diets. The antihypertensive effect of supplemental calcium was associated with a 39% reduction in systemic vascular resistance. Therefore, dietary calcium supplementation lowers blood pressure in 2-K, 1C RVH primarily due to a systemic vasodilatation and reduced vascular reactivity to moderate doses of norepinephrine.

Mechanism of decreased vascular response to angiotensin II in renal vascular hypertension.

Compared to many forms of hypertension, vascular reactivity to angiotensin II (AII) is decreased in the early phase of two-kidney, one clip (2-K, 1C) renovascular hypertension (RVH). To determine the role of the AII receptor, we examined vascular responsiveness and 125I-AII binding to mesenteric artery membrane fractions after three weeks of 2-K, 1C RVH. Systolic blood pressure was 165 +/- 8 in RVH and 105 +/- 4 mm Hg in controls, P less than 0.001. Plasma renin activity was 4.2 +/- 0.6 in RVH and 1.4 +/- 0.5 ng AI/ml/hr in controls, P less than .001. The pressor response to exogenous AII was reduced by 40% in RVH. Since administration of a single dose of converting enzyme inhibitor (CEI) did not normalize the response to exogenous AII, the decreased reactivity was not caused by receptor occupancy. 125I-AII binding to mesenteric arteries was equal to or greater in RVH than controls at all concentrations of AII. Scatchard analysis revealed an increase in the total number of binding sites (BMAX): 140.8 +/- 6.3 in RVH versus 91.7 +/- 6.5 fmol/mg in controls, P less than 0.01, while the apparent dissociation constant was unchanged. To determine if the increase in circulating AII caused these binding alterations, rats were either treated with CEI for three days; or unilaterally nephrectomized. Both of these manipulations reversed the decrease in vascular responsiveness as well as the increase in receptor number (BMAX = 136 +/- 13.4 in RVH vs. 94 +/- 9.4 fmol/mg in RVH + nephrectomy, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of intensive dialysis in acute renal failure.

The efficacy of vigorous dialysis in the management of acute renal failure remains controversial. In order to examine the beneficial role of vigorous dialysis, a prospective study was carried out in 34 patients paired by acute renal failure etiology and treated with sufficient dialysis to maintain predialysis blood urea nitrogen and serum creatinine below either 60 and 5 mg/dl (intensive) or 100 and 9 mg/dl, respectively (non-intensive). Serum creatinine was at least 8 mg/dl in all patients prior to random assignment to intensive or non-intensive dialysis. Mean predialysis blood urea nitrogen and serum creatinine, respectively, were 60 +/- 23 and 5.3 +/- 1.5 mg/dl in the intensively dialyzed group and 101 +/- 18 and 9.1 +/- 1.4 mg/dl in the non-intensively dialyzed group (both p less than .001). Predialysis serum bicarbonate and blood pH were lower and serum phosphate higher in the non-intensively dialyzed patients. Daily weight changes, increases in blood urea nitrogen, protein and calorie intakes were similar. While hemorrhagic episodes tended to be more frequent in non-intensively dialyzed patients, overall complication rates were not different between the two groups. Mortality rates, which were 58.8% in the intensive and 47.1% in the non-intensive groups, also were not different. On the other hand, urine output prior to dialysis did influence survival. It is concluded that, within the limits of the study, there is no advantage to intensive dialysis in the management of acute renal failure.

Effect of potassium depletion on two-kidney, one-clip renovascular hypertension in the rat.

There is considerable controversy about the hemodynamic effect of potassium in hypertension. To determine if K depletion could alter the control of blood pressure, studies were performed in rats with 2-kidney, 1-clip renovascular hypertension (RVH) after 3 to 6 wks of severe and moderate K depletion. After application of a 0.23 mm clip to the left renal artery, rats were placed on a K-replete (KR) (240 mEq/kg), a moderately K-depleted (KDM) (59 mEq/kg), or a severely K-depleted (KDS) (5 mEq/kg) diet. After 3 wks, mean arterial pressure (MAP) reached 154 +/- 3 in KR but only 121 +/- 2 in KDM (P less than 0.01) and 106 +/- 4 mm Hg in KDS (P less than 0.001). After 6 wks, MAP was 160 +/- 8 in KR, but only 132 +/- 5 in KDM (P less than 0.01) and 129 +/- mm Hg in KDS (P less than 0.01). Plasma K at 3 wks was 4.1 +/- .1 in KR, but only 3.5 +/- .1 in KDM (P less than 0.05) and 2.3 +/- .1 mEq/liter in KDS (P less than 0.001). This was associated with an 8% decrease in muscle K in KDM and a 16% decrease in muscle K in KDS. Although KDS animals did not grow during the 6 wks of study, KDM rats gained 60% as much weight at 3 wks, and, by 6 wks, weight gain was comparable in KDM (101 +/- 9) and KR (110 +/- 9 g) animals (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Nephrotoxicity following single dose mithramycin therapy.

Mithramycin given as a single dose for the treatment of hypercalcemia has not been reported to cause renal dysfunction. A case is presented of nephrotoxicity following a single 25 micrograms/kg dose in a patient with underlying squamous cell carcinoma, obstructive uropathy, and hypercalcemia. Underlying renal impairment may magnify the nephrotoxicity of mithramycin.