A. C. Corcoran

A Mechanism of Chlorothiazide-Enhanced Effectiveness of Antihypertensive Ganglioplegic Drugs

Chlorothiazide decreases plasma volume, heart size, and cardiac output. The oligemia stimulates vasomotor tone; this tends to maintain arterial pressure because chronic arterial hypertension is characteristically self-sustaining and homeostatic. This oligemic stimulation of vasomotor tone results in increased sensitivity to the antihypertensive effect of drugs depressing or blocking vasomotor function.

Controlled Observations on the Effect of Low Sodium Dietotherapy in Essential Hypertension

The effectiveness and practicality of low sodium diets are tested in groups of in- and outpatients. The data indicate that roughly one-fourth with severe essential hypertension can respond favorably to prolonged restriction of sodium intake to less than 0.5 Gm. daily. The rice diet is found to be in effect a simple low sodium diet. Under the conditions of outpatient practice, low sodium dietotherapy is usually impractical and must be controlled by frequent analyses of urinary sodium.

Atherosclerosis and the Fat Content of the Diet

A report to the American Heart Association and to the American Society for the Study of Arteriosclerosis the Nutrition Committee of the Council on Community Service and Education of the American Heart Association and others.

The Effectiveness of Long-Term Treatment of Malignant Hypertension

A survey is reported of the courses of 84 patients who presented the syndrome of malignant hypertension and who have been under treatment with potent antihypertensive drugs. Among these, 70 per cent survived 1 year of observation, 50 per cent 3 years, 33 per cent 5 years, and 26 per cent 6 years. These survival rates represent substantial therapeutic gains over survival rates in the untreated series of Keith, Wagener, and Barker. The reported first-year survival rate is weighted by the untoward complication of hexamethonium pneumonitis, and current survival is greater than in the estimate presented. Other causes of death are (1) rapidly or (2) delayed or slowly progressive renal failure and (3) complications of atherosclerosis. The first is usually associated with poor control of blood pressure. It seems merely an attenuation of the usual course of malignant hypertension. The syndrome of delayed or slowly progressive renal failure is associated with diffuse occlusive fibrous intimal hyperplasia of major renal arteries. Among the complications of atherosclerosis, cerebral hemorrhage was the most common and was associated with poor control of blood pressure level, while myocardial infarction, the next most common, was not. It may be that the coronary arteries, like the renal, are subject to progressive occlusive disease in some patients with treated malignant hypertension. It is not clear whether this process represents a continuation in vessels larger than arterioles, of a basic vascular disease or a delayed response on the part of the arteries to preexisting severe hypertension. Survival is improved in patients who undertake treatment before malignant hypertension has caused extensive vascular damage. Patients who present themselves for treatment with evidences of severe renal damage generally do not survive for long periods. However, several such have maintained active lives for many months and years. Hence treatment should be withheld only in the most desperate circumstances.

Functional patterns in renal disease.

Excerpt The introduction of procedures by Homer Smith which permit the measurement of minimal renal blood and plasma flow, glomerular filtration rate and tubular secretory capacity has enabled meas...

Effects of Serotonin Antagonists in Normal Subjects and Patients with Carcinoid Tumors

The pathogenesis of flushing attacks in patients with malignant carcinoid tumors is attributed to the direct pharmacologic effect of excessive amounts of circulating serotonin. It was hoped that potent serotonin antagonists might relieve symptoms of the carcinoid syndrome in the inoperable patient. The nature of flushing attacks was studied in carcinoid patients and the influence thereon of 3 serotonin antagonists, a benzyl analog of serotonin, bromo-lysergic acid diethylamide, and chlorpromazine. The systemic, subjective, and vascular effects of these antagonists in normal subjects were also investigated.

Separated renal functions in patients with renal arterial disease, pyelonephritis, and essential hypertension.

Function tests of the individual kidneys have been performed during mannitol diuresis and vasopressin infusion in hypertensive patients with essential hypertension, pyelonephritis, and occlusive lesions of one or both main renal arteries or their primary branches. In patients with essential hypertension, glomerular filtration rate and renal plasma flow on the two sides, though depressed, were practically equal, as were urine flow, water, solute, and sodium excretions. Pyelonephritis and branch arterial lesions alike depressed urine flow, glomerular filtration rate, and renal plasma flow in the affected or more-affected kidneys; water, total solute, and sodium excretions were in proportion to glomerular filtration rate. These findings indicate a decrease in numbers of functioning nephrons without a qualitative change in function of those remaining. Occlusive lesion of one main renal artery decreased glomerular filtration rate and renal plasma flow on the affected side; urine flow was relatively more depressed than filtration rate, urinary osmolality was higher, and urinary sodium concentration was sharply decreased, as was the excreted fraction of the filtered sodium load. Bilateral occlusive main arterial lesions sometimes had effects similar to those of unilateral lesions in the sense of greater functional deficits on the more-affected sides. However their functional patterns were not consistent. The enhanced renal sodium reabsorption observed in patients with unilateral and bilateral main renal artery diseases could not be explained solely by decreases in filtered sodium load; this suggests that decreases in intrarenal arterial pressure also affect sodium excretion. Changes in renal functions caused by arterial disease depend on the site of the lesion and not on the pressor mechanism it may evoke.

Management of hypertensive disease.

Abstract 1.1. The pharmacotherapy and management of severe hypertensive disease are reviewed primarily with regard to hydralazine and hexamethonium. The former gives sustained relief and decreases mortality in about half of the patients treated; its use is complicated by common, usually transitory side-effects and, in some patients, by a delayed toxic response characterized as a rheumatic and febrile syndrome. 2.2. Experience with the use of hexamethonium alone shows that it gave temporary relief in sixteen of seventeen patients with malignant hypertension; the duration of relief was limited by tolerance to its depressor effect on supine diastolic pressure. Benefit was not determined by persistence of orthostatic hypotension. 3.3. Some additive effects of combined treatment with hexamethonium and hydralazine were defined in seven of fourteen patients tested with these drugs separately and in combination. However, only two gained more than ten mm. Hg decrease in average supine diastolic pressure from the combination. Side-effects of hydralazine were not mitigated by effective doses of hexamethonium. 4.4. Preliminary observations indicate that reserpine (serpasil ® ) is a potent antipressor in some patients when used alone or in association with other drugs. 5.5. In perspective, the considerable efficacy of specific agents and procedures in some patients, but not in others, suggests that hypertension in these is sustained by different, definable mechanisms. Insight into these should diminish the large measure of poorly rationalized empiricism which presently clouds the treatment of hypertensive disease.

Effects of Chlorothiazide on Specific Renal Functions in Hypertension

Oral administration of chlorothiazide depresses glomerular filtration, increases blood urea, maintains sodium output in the face of decreased filtered sodium load, and paradoxically for a diuretic, in these and in tests done shortly after intravenous administration, increases the efficiency of water reabsorption.

Vascular Reactivity of Rats and Dogs Treated with Desoxycorticosterone Acetate.

Summary Chronic treatment with DCA of dogs and rats, does not increase significantly vascular response to epinephrine, renin and angiotonin to explain DCA-hypertension on the basis of vascular hypersensitivity.