We examined the chronic effects of losartan (DuP 753), a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in eight hospitalized patients with essential hypertension. After a control period of 1 week, losartan was administered orally once a day for 2 to 4 weeks in increasing doses of 12.5, 25, 50, and 100 mg, until blood pressure in the supine position decreased more than 20 mm Hg (systolic) and 10 mm Hg (diastolic) (or 13 mm Hg in mean blood pressure). The average dose of losartan was 59.4 +/- 43.7 (mean +/- SD) mg/day. Systolic, diastolic, and mean blood pressures, according to 24 h monitoring, fell significantly, from 151.9 +/- 6.8 to 137.2 +/- 7.9 mm Hg, from 90.6 +/- 3.7 to 81.0 +/- 3.7 mm Hg, and from 111.1 +/- 4.6 to 99.7 +/- 5.0 mm Hg, respectively (mean +/- SE, P < .01 for each), with no change in circadian rhythm or variability of blood pressure. Reduction in blood pressure was slightly greater during daytime than during sleep time. Unlike peptide angiotensin II antagonists, losartan did not exert pressor action. No significant alterations were observed in body weight, serum electrolytes, creatinine clearance, urine volume, or urinary excretion of sodium. Losartan significantly lowered serum uric acid concentration from 5.5 +/- 0.4 to 4.8 +/- 0.3 mg/dL (P < .05). Urinary excretion of uric acid increased significantly from 498.9 +/- 64.4 to 540.6 +/- 66.6 mg/day (P < .05). Plasma renin activity rose significantly but plasma aldosterone concentration did not change with the losartan treatment. These results suggest that losartan has a long-acting hypotensive effect with a hypouricemic action in essential hypertension.

We investigated whether treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (erythropoietin) for a short period would increase their blood pressure. Ambulatory blood pressure monitoring and home blood pressure measurements were used to detect minute increase in blood pressure. Thirty-two patients with a hematocrit of 25% or less received erythropoietin at the dose of 4500 IU/week, by the intravenous route for 8 weeks. Erythropoietin increased the hematocrit from 20.9 +/- 2.1 to 26.2 +/- 2.1%. Erythropoietin elevated mean ambulatory blood pressure by 5 mmHg or more in two-thirds of patients (n = 20; pressor group), while it elevated home mean blood pressure by 5 mmHg or more in one-third of patients (n = 11). An increase in clinic mean blood pressure by more than 5 mmHg was observed only in one-fourth of patients (n = 7). Circadian variation of blood pressure (nocturnal fall and diurnal rise) had been attenuated in the patients of the pressor group before erythropoietin treatment and erythropoietin decreased the nocturnal fall of blood pressure further more. Erythropoietin elevated nocturnal blood pressure more than diurnal blood pressure. Therefore, the increase in blood pressure induced by erythropoietin was detected more reliably by ambulatory blood pressure monitoring. There was no relation between the change in hemoglobin concentration and the increase in ambulatory blood pressure induced by erythropoietin. Erythropoietin tended to decrease cardiac output and plasma volume while it increased total peripheral resistance. It also decreased plasma norepinephrine and vasopressin levels but did not affect other humoral factors. Although the pressor effect of erythropoietin treatment for 8 weeks at the dose of 4500 IU/week was not evident on clinic blood pressure measurements, any increase in blood pressure determined by ambulatory blood pressure should be treated carefully to reduce the risk of a cardiovascular complication in patients receiving hemodialysis.

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The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.