Herbert G. Langford

Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. The TAIM Research Group.

The Trial of Antihypertensive Interventions and Management is a multicenter randomized trial designed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90-100 mm Hg). Eight hundred and seventy-eight participants at 110-160% of ideal weight were randomly allocated to nine drug/diet treatment groups receiving either a placebo, chlorthalidone (25 mg), or atenolol (50 mg), combined with a usual, a weight loss, or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months. Seven hundred and eighty-seven participants had follow-up data. The mean baseline diastolic blood pressure was 93.8 mm Hg; 55.9% of the participants were male, and the weight loss diet group lost an average of 4.7 kg. Multiple comparisons were accounted for in the analysis. A significantly greater lowering of diastolic blood pressure (12.4 mm Hg) was achieved in the atenolol group compared with either the low sodium/high potassium diet group (7.9 mm Hg, p=0.001) or weight loss group (8.8 mm Hg, p=0.006). Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering (15.1 mm Hg) when compared with the diuretic alone (10.8 mm Hg, p=0.002), but adding a low sodium/high potassium diet (12.2 mm Hg, p=0.029) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration, drugs outperform diet, and weight loss is beneficial, especially with diuretics.

Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies

The antihypertensive effects of intravenous labetalol were evaluated in 59 patients with hypertensive crises or severe hypertension in need of rapid lowering of blood pressure in a multicenter study. Patients appearing with a supine diastolic blood pressure 125 mm Hg or greater, or a supine systolic blood pressure of more than 200 mm Hg received an initial mini-bolus injection (20 mg) of labetalol. This was followed by repeated incremental doses of 20 to 80 mg given at 10 minute intervals to achieve a supine diastolic blood pressure of less than 95 mm Hg or decrease 30 mm Hg or greater, or a satisfactory decrease in systolic blood pressure. Patients were stratified into those who had taken antihypertensive medication within 24 hours and those who had not. The initial mini-bolus injection caused rapid but not abrupt reduction in blood pressure; the baseline mean blood pressure decreased 23/14 mm Hg. Further injections were needed in the majority of patients (mean: 197 mg). The blood pressure reduction after the last dose of labetalol was 55/33 mm Hg. In pretreated patients and in those who had no medication for 24 hours prior to the intravenous labetalol, the response was similar. Heart rate decreased 10 beats per minute in the total population. In patients pretreated with beta-adrenergic blockers, blood pressure response was similar to that in the total group (59/35 versus 55/33 mm Hg), but heart rate remained essentially unchanged. The dose required to achieve the therapeutic effect was less in pretreated patients than in untreated patients, but the duration of action was shorter. No serious adverse effects were encountered even in patients with concomitant diagnoses of acute left ventricular failure, myocardial infarction, stable congestive heart failure, atrial fibrillation, angina pectoris, acute stroke, transient ischemic attack or encephalopathy. Labetalol is a safe and effective treatment for a rapid blood pressure reduction in hypertensive emergencies.

Trial of antihypertensive intervention and management: Greater efficacy with weight reduction than with a sodium-potassium intervention

The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive, moderately obese participants using a 3 x 3 factorial design. Drugs evaluated were placebo, diuretic (chlorthalidone), and beta-blocker (atenolol); diets were usual (no intervention), weight reduction, and low sodium/high potassium (Na/K). This article reports 6-month dietary changes and the effect of dietary change on blood pressure. Six-month mean weight change was -4.7 kg in the weight reduction group, -0.3 kg in the Na/K group, and -0.5 kg in the usual-diet group. At 6 months, daily electrolyte excretion had changed in the Na/K intervention group. Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group. Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group, from 57.0 to 60.5 mmol in the weight reduction group, and from 55.3 to 59.1 mmol in the usual diet group. Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol. Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification.

Response of Mineralocorticoid Hypertensive Animals to an Angiotensin I Converting Enzyme Inhibitor

Summary The effect of the angiotensin I converting enzyme inhibitor, SQ-14,225 on DCA-NaCl hypertension was determined. The inhibitor did not affect the development of DCA-NaCl hypertension. It also did not affect the blood pressure of animals with established DCA-NaCl hypertension. This suggests that the SQ-14,225 exerts its antihypertensive effect purely by decreasing angiotensin II and not by increasing vasodilator kinins.

The effect of cimetidine and propantheline on the symptoms of a patient with systemic mastocytosis

A 24 year old white woman with a lifelong history of systemic mastocytosis and symptoms of diarrhea and flushing was demonstrated to have a normal gastric analysis and inconsistent steatorrhea. She responded well to oral cimetidine therapy for 11 months. A symptomatic recurrence was controlled with the addition of propantheline. Gastric secretory studies demonstrated cimetidine suppression of both basal acid and basal pepsin secretion, as well as maximal pentagastrin-stimulated acid secretion; suppression of stimulated pepsin secretion was minimal. The combination of cimetidine and propantheline markedly suppressed both peak acid and peak pepsin secretion in response to pentagastrin stimulation. These data support a dominant role of cholinergic mechanisms in the control of gastric pepsin secretion; additional data obtained with maintenance of constant intragastric pH are required for further clarification.

Diuretic Effect of Angiotensin in the Chicken.

Summary One group of chickens infused into the renal portal vein showed more water and sodium excreted from the experimental side, though bilateral diuresis occurred. In another group G.F.R.

Dietary approaches to the reduction of blood pressure: The independence of weight and sodium/potassium interventions

This study was designed to determine the feasibility of teaching mildly hypertensive individuals to select a diet, using normally available food products, that either would produce a 5% reduction in percentage of overweight (without altering sodium (Na), potassium (K), or Na:K ratio) or would decrease Na to less than 70 mEq and increase K to greater than 100 mEq (without affecting weight) and to compare the resulting changes in blood pressure. Fifty-two participants with mild hypertension were randomly assigned to either a weight-loss or a Na:K intervention. Blood pressure, weight, 3-day diaries, and 24-h urinary excretion of Na and K were measured before and after an 8-week intervention. Participants in the weight-loss intervention had significantly greater changes in weight and calorie intake than those in the Na:K intervention, while changes in Na:K ratio were greatest in the intervention targeted for that change. The percentage of participants who were able to meet the dietary goals is presented and the implications of these data for the selection of dietary goals are discussed.

Angiotensin and salt appetite: physiological amounts of angiotensin given peripherally increase salt appetite in the rat

Two experiments were conducted in which adrenalectomized male Sprague-Dawley rats were maintained ad lib on distilled water, 3% saline, and sodium-free food. In Experiment 1, 45 rats were given 100, 200, 400, 800, and 1,000 micrograms/kg/day desoxycorticosterone acetate (DOCA) im for 5 days to determine the dose of DOCA that would produce the lowest voluntary saline intake, and 800 micrograms/kg/day was found to produce the nadir in saline intake. In Experiment 2, 40 rats were placed ad lib on distilled water, saline, and sodium-free food as described above, maintained on 800 micrograms/kg/day DOCA, and infused with 4, 25, 100 micrograms/kg/day angiotensin II (A II) or 0.9% saline. The three A II groups showed significant percentage changes in their saline intake above pre-A II levels; the saline control group showed no change in saline intake from pre-A II level. These results are interpreted to demonstrate the production of salt appetite in rats by peripheral administration of physiological doses of angiotensin II.

Effect of hypervolemia and elevated arterial pressure on circulatory dynamics of pregnant animals

Abstract In an attempt to gain insight into some of the mechanisms which may underlie the changes in the circulatory system that accompany pregnancy, the effect of hypervolemia and elevated arterial pressure on the mean circulatory pressure was studied. There was a linear relationship between mean circulatory pressure and blood volume and the mean circulatory pressure increased when the arterial pressure was elevated. These data indicate that hypervolemia is responsible for some of the hemodynamic alterations which accompany pregnancy.

Thiazide versus placebo in prophylaxis of toxemia of pregnancy in primigravid patients

Abstract Eighty normal primigravid patients in the second trimester of pregnancy were given either placebo or hydrochlorathiazide daily until delivery. There was a significant difference in the incidence of pre-eclampsia in the two groups. When the two groups were further divided into those with blood pressure elevation over 12070 and those under, it was felt that the most progress was made in the group in whom the blood pressure exceeded this level.