Salt and blood pressure responses to calcium antagonism in hypertensive patients.

Since salt intake may affect blood pressure response to antihypertensive drugs, an individual's salt-sensitivity status may be an important consideration in the selection of a medication. The purpose of this single-blind study was to assess the impact of salt sensitivity on the antihypertensive effects of isradipine. A total of 21 evaluable hypertensive patients (10 white, 11 black) 35 to 73 years of age (mean 55.9 years) were randomized to a low-salt diet (mean 24-hour urine sodium 100+/-14 mmol) or a high-salt diet (mean 24-hour urine sodium 210+/-22 mmol) for 7 weeks, followed by crossover to the other diet after a 2-week washout period. On each diet regimen, patients received placebo for 2 weeks, followed by optimal titration of isradipine (2.5 to 10 mg BID) for blood pressure control during the last 5 weeks. On the high-salt diet, salt-sensitive hypertensives (mean arterial blood pressure increase > or = 5 mm Hg, n=5) exhibited a systolic/diastolic blood pressure change of -18.7/-19.6 mm Hg from 157.2/102.9 mm Hg after 5 weeks of isradipine treatment, whereas on a low-salt diet, blood pressure change was -6.9/-12.0 mm Hg from 148.7/97.3 mm Hg. Non-salt-sensitive patients (n=16) exhibited a systolic/diastolic blood pressure change of -12.6/-7.6 mm Hg from 155.3/98.6 mm Hg on the high-salt diet and -19.2/-10.9 mm Hg from 161.0/102.6 mm Hg on the low-salt diet after treatment with isradipine. The absolute blood pressure attained in both salt-sensitive and non-salt-sensitive patients was almost identical with isradipine therapy despite variation in dietary salt, although slightly higher doses of isradipine were required in the salt-sensitive group. Consequently, isradipine, and perhaps calcium antagonists in general, manifests a more robust blood pressure-lowering effect in the setting of high sodium intake. This effect does, however, appear to be largely confined to individuals who are salt sensitive.

A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients.

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.

Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria.

Nine white and 13 black hypertensive patients with normal serum creatinine were randomized to receive either 2 weeks of a low-salt (40 mEq Na+/d) or high-salt (200 mEq Na+/d) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet. The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collections of urine for analysis. Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced (100 +/- 14 mEq Na+/24 h [mean +/- SEM]) low-salt diet as outpatients, while the higher-salt diet (236 +/- 22 mEq Na+/24 h) was more easily achieved. Eleven patients (8 black, 3 white) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets, respectively. In the salt-sensitive patients, the increase in dietary salt intake increased glomerular filtration rate by 29% (71.2 +/- 6.6 to 85.8 +/- 7.3 mL.min-1.1.73 m2, P = .05), with no significant change in renal plasma flow (412.7 +/- 36.4 to 399.6 +/- 27.8 mL.min-1.1.73 m2). There were no changes in these parameters in the salt-resistant patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor receptor regulation in rat kidney: two models of renal growth.

The binding of 125I-labeled epidermal growth factor (EGF) to plasma membranes prepared from rat kidney cortex was studied following unilateral nephrectomy, a model of proximal tubule cell hypertrophy, and following the administration of folic acid, a model of proximal tubule cell hyperplasia. Binding of 125I-EGF was a linear function of basolateral membrane protein content and time of incubation. Specific binding to luminal brush-border membranes was not evident in these studies. Neither insulin nor insulin-like growth factor I could displace EGF binding, indicating that binding was specific. Scatchard analysis revealed a single binding site. The KD in sham-operated animals 48 h after surgery was 11.2 +/- 1.4 nM, whereas Bmax averaged 95.2 +/- 4.1 fmol/mg protein (n = 3). Similar values were obtained in nephrectomized animals. The Bmax of folic acid-untreated animals averaged 212.5 +/- 6.9 fmol/mg 48 h after administration, whereas that of vehicle-injected controls averaged 85.4 +/- 9.2 (n = 3, P less than 0.001). Differences in binding were not related to changes in affinity, ligand degradation by the preparations, or receptor binding of endogenous EGF. These data indicate that regeneration following folic acid administration is associated with an upregulation of proximal nephron EGF receptors that may play an important role in the mitogenic response.