Influence of circulating insulin-like growth factor-I compared with that of intrarenal insulin-like growth factor-I on proximal nephron receptor density in rats.

1. We examined the effects of dietary protein manipulations in partially nephrectomized (one and one-third nephrectomy) and normal rats to gain perspective on the relative importance of circulating versus intrarenal (collecting tubule) insulin-like growth factor-I in the control of proximal nephron receptor density. In addition, we studied the factors that influence liver insulin-like growth factor-I secretion in partially nephrectomized rats. 2. Dietary protein restriction (6% versus 40%) lowered circulating levels of insulin and insulin-like growth factor-I in both normal and partially nephrectomized rats up to 3 weeks after institution of the diets; however, growth hormone levels were little changed. Reduced renal mass stimulated intrarenal production of insulin-like growth factor-I regardless of the diet. 3. Scatchard analysis revealed that the density of insulin-like growth factor-I receptors on glomerular and proximal tubule basolateral membranes increased when circulating levels of insulin-like growth factor-I were diminished, despite raised levels of intrarenal insulin-like growth factor-I, in partially nephrectomized rats. 4. Circulating insulin-like growth factor-I, rather than the tissue level, plays the dominant role in the control of proximal nephron receptor density under physiological conditions. Insulin, but not growth hormone, may play a role in liver insulin-like growth factor-I secretion in partially nephrectomized rats during dietary manipulations.

Intravascular retention and renal handling of purified natural and intramolecularly cross-linked hemoglobins.

Plasma half time of unmodified hemoglobin (UHb) and two intramolecularly cross-linked hemoglobins (alpha alpha XL and beta beta XL) was measured in anesthetized rats after an intravenous bolus of 20 mg.100 gm.-1 To rule out the possibility that differences among plasma half times might be caused by differences in acute effects on renal excretory function, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with plasma half time. Experiments were also done to determine whether higher doses (60 to 100 mg-1.100 gm-1) of these compounds had a delayed effect (48 hours) on GFR or ERPF. Massive urinary excretion of UHb occurred; however, only 1% of the alpha alpha XL and none of the beta beta XL was excreted. Plasma half time of alpha alpha XL and beta beta XL averaged 3.3 hours, or four times longer than UHb. In no case did a decrease in GFR or ERPF occur. Instead, a transient increase in GFR, ERPF, urine flow, and systemic blood pressure was seen. Similar increases occurred after albumin administration, suggesting expansion of vascular volume as the initiating factor. Renal functions at 48 hours after 60 to 100 mg.100 gm-1 of UHb, alpha alpha XL or beta beta XL were not different from control (albumin). Intratubular hemoglobin casts or intravascular precipitates were not evident in acute or 48-hour studies. At 48 hours Perls' staining material was found in one alpha alpha XL specimen at 3 hours after administration. Perls' staining material was present in renal tubule cells in all but the albumin-treated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of calcium channel blockers on in vivo cellular immunity in mice.

In vitro studies have shown that calcium channel blockers (CCB) inhibit lectin-induced lymphocyte proliferation. However, no in vivo effects have been documented yet. In this study we evaluated the effects of CCB on in vivo cellular immunity by using contact sensitivity to oxazolone in mice. From 15 to 30 twelve-week-old female C3H mice were randomized into: 0.9 NS (sham), ethanol, CsA, dexamethasone (DXM), verapamil, diltiazem, and nifedipine groups. These study agents were given daily from day 1 to day 9 subcutaneously to the shaved abdominal wall. The mice were sensitized with oxazolone to the abdominal wall on day 2 and challenged with oxazolone on the right ear on day 8. Delayed-type hypersensitivity was measured on day 10 and defined as the difference in thickness between the right (challenged) and left (control) ear of each mouse. The mean DTH of each study group was compared with that of the sham, and the statistical significance was determined by a Student's t test. The percentage of change in DTH from the sham was also calculated as: (mean DTH of study drug group-mean DTH of sham group)/mean DTH of sham group x 100%. A negative value meant a suppressive effect on DTH; a positive value, an enhancing one. The CsA, DXM, and nifedipine all had significant suppressive effects on DTH. Verapamil had a significant enhancing effect. Ethanol and diltiazem had no significant effect. More studies employing other antigens with several other cell-mediated response measurements along with DTH quantification should be done in order to determine the specificity of the immunosuppressive effect of CCB as well as the potential of any calcium antagonist as an adjuvant suppressive agent.