Combined use of nifedipine and diltiazem for the treatment of severe hypertension.

Calcium channel blockers are a heterogeneous group of drugs that have enhanced our ability to concurrently control blood pressure, treat coronary artery disease, and avoid many of the side effects of previously available antihypertensive agents. Patients with severe hypertension may require multiple agents for adequate control of blood pressure because of either poor control with one agent or side effects from high doses of a single agent. Laboratory investigations have shown a synergistic effect on receptor binding, as well as increased drug levels with the concurrent use of diltiazem and a dihydropyridine calcium channel blocker (nifedipine or nicardipine). It is as yet unknown whether these effects on receptor binding and increased drug levels translate into greater clinical efficacy in blood pressure control. We have reported what we believe to be the first case in which this interaction was used successfully to control previously poorly controlled hypertension, while minimizing side effects.

Renal acidification in sickle-cell disease.

Renal acidification was evaluated in patients with sickle-cell disease (HvSS) with both oral NH4CI and NaHC03 and the results were compared to those of subjects with sickle-cell trait (HbAS) and controls. The pH of arterial blood was normal in HbSS subjects but their PC02 and [HC03] were lower than those of controls. In response to NH4CI, six of 20 HbSS subjects had an abnormal minimal urine pH (greater than 5.3) and the entire HbSS group had a higher mean value than did either controls or HbAS subjects. Since none of the six HbSS subjects had evidence of proximal tubular abnormalities, it was concluded that they exhibited the syndrome of incomplete distal renal tubular acidosis. Only one of the six HbSS volunteers with an abnormal response to NH4CI and two of seven with a normal response increased their urinary PC02 normally after bicarbonate loading. PAH clearance was significantly higher and inulin clearance tended to be higher in HbSS subjects than in either controls or HbAS subjects. Maximal concentrating ability was decreased in both sickle-cell groups but more so in HbSS. No adverse effects occurred and no appearance or increase in per cent of sickled cells resulted from short-duration NH4CI acid-loading. No differences were found either in the clinical characterstics or in hematological, renal, and acid-base variables between the HbSS subjects with and without a normal response to acid-loading. The mechanism for the observed renal acidification abnormality remains unknown.

Renal acidification in sickle cell trait.

Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups. After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics.

Impaired renal tubular reabsorption of sodium in hypothyroid man.

The renal response to acute salt loading and to stimuli for rapid sodium conservation was studied in 14 patients with untreated myxedema and in 13 euthyroid control subjects in balance on a 155 mEq. sodium intake. The salt-loading studies reveal urinary excretion of sodium in the myxedema patients within the range of controls despite reductions of 34 per cent in glomerular filtration (p less than 0.001) and 37 per cent in filtered load of sodium (p less than 0.001) in the former group. The capacity to conserve sodium in response to stimuli for rapid sodium conservation [postural change and administration of a supramaximal dose of 9alpha-fluorohydrocortisone (9alpha-F)] was impaired in patients with myxedema. The per cent decrease in sodium excretion during the upright posture in the hypothyroid patients was 28 per cent, less than half that observed in the control subjects, 62 per cent (p less than 0.005). Following administration of 2 mg. of 9 alpha-F the per cent decrease in sodium excretion was less (p less than 0.05) in the hypothyroid patients (50 per cent) than in control subjects (72 per cent). In all studies, baseline sodium excretion was comparable in both groups. Fractional excretion of sodium was significantly increased in the hypothyroid patients prior to (p less than 0.005) and during saline loading (p less than 0.05) and at the time of the subnormal responses to stimuli for acute sodium conservation (p less than 0.05 less than 0.005). Potassium excretion was reduced in the hypothyroid patients, even after 9alpha-F. These observations indicate decreased tubular reabsorption of sodium in myxedema under the experimental conditions described. The findings are most consistent with a role for thyroid hormone in normal sodium reabsorption. That this is not related to mineralocorticoid deficiency is suggested by the impaired sodium reabsorptive response to 9alpha-F.