Short-term therapy of severe hypertension. Hemodynamic correlates of the antihypertensive response in man.

Ten severely hypertensive patients were randomized into five treatment groups: vasodilators; vasodilators plus diuretics; sympatholytics; sympatholytics plus diuretics; and sympatholytics, diuretics, and vasodialtors. Cardiac index was measured daily by echocardiography, and total peripheral resistance (TPR) calculated. Plasma renin activity (PRA) and creatinine clearance (CCR) were measured every other day. There was no difference in antihypertensive response. Seven patients, whose initial TPR was high, responded to treatment with a fall in TPR, regardless of regimen. Three patients with a high pretreatment cardiac index responded with a fall in cardiac index. Changes in TPR or cardiac index were not related to changes in CCR. There was no correlation between PRA and either blood pressure or TPR. It is concluded that the pretreatment hemodynamic status of severely hypertensive patients is the major determinant of the hemodynamic response to antihypertensive therapy.

The effect of diet on echocardiographic left ventricular dimensions in normal man.

The effect of dietary sodium and potassium on echocardiographic left ventricular dimensions was studied in normal subjects. In 10 subjects, left ventricular end diastolic volume was found to be 18.8 greater, and systolic volume 17.1% higher with zoo mEq sodium diet than on a 1Omeq sodium diet (P less than 0.025). While receiving an ad libitum diet, the subjects were found to have an end diastolic volume of 107.9 +/- 6.4 ml SE and an end systolic volume of 45.2 +/- 2.7 ml SE. During sodium depletion, values fell to 101.3 +/- 5.7 ml SE and 38.6 +/- 2.9 ml SE, respectively, then on a high sodium diet rose to 120.3 +/- 7.0 ml SE and 45.2 +/- 2.7 ml SE, respectively. Heart rate fell during sodium repletion by 4.2% (P less than 0.05) while mean arterial blood pressure, cardiac output and peripheral vascular resistance did not change significantly. In contrast, seven subjects consuming a diet containing 25 and 200 mEq potassium in seqeucne, the sodium intake remaining constant, did not display significant changes in cardiac dimension, heart rate, blood pressure, cardiac output, or vascular resistance. It is concluded that dietary sodium significantly effects the size of a nonfailing left ventricle, an effect that must be considered when single or sequential echocardiograms are interpreted.

SQ 20,881: effect on eclamptic--pre-eclamptic women with postpartum hypertension.

The renin-angiotensin system has been implicated in the genesis of pre-eclampsia. To avoid fetal toxicity, five women were studied who developed hypertension, proteinuria, and edema in the last trimester of pregnancy and whose BP elevation persisted immediately postpartum. At about 6 hours after delivery the CE enzyme inhibitor (SQ 20,881) was given in incremental doses ranging from 0.25 to 3.0 mg. per kilogram intravenously, before and after diuresis with furosemide, 40 mg. intravenously. BP was measure every 2 minutes and PRA and angiotensin II concentration before treatment, 30 minutes after 0.25 to 0.30 mg. per kilogram, and 30 minutes after 2.0 to 3.0 mg. per kilogram. Echocardiographic assessment of CI and PVR was performed before treatment and after a maximum dose in three patients. Before diuresis, CE blockade had no effect on heart rate, BP, CI, PVR, or PRA, regardless of whether the patient was in positive or negative fluid balance or was sodium loaded or restricted over the preceding 24 hours. Angiotensin II fell by 77 and 10 per cent, respectively, after 0.25 mg. per kilogram was given to two patients, but rose slightly in the other three patients, then fell an average of 46 per cent after 1.0 to 3.0 mg. per kilogram were given. After diuresis, 1.0 mg. per kilogram resulted in a 24 per cent fall in BP which persisted for 3 hours in two patients and a 14 per cent fall which lasted for 30 minutes after 1.0 or 3.0 mg. per kilogram in a third patient. It is concluded that the BP elevation which persists after delivery in certain patients with pre-eclampsia is not angiotensin II dependent.