We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.

The mechanism of recumbent hypertension induced by fludrocortisone was studied in seven patients with orthostatic hypotension. All showed increases in blood pressure in the recumbent and standing positions, and hypertensive levels were achieved on recumbency in four of them. Hypertensive retinopathy developed in two patients and cardiomegaly in one. Initial blood-pressure elevations were associated with sodium retention and plasma-volume expansion. However, with long-term treatment, plasma volume decreased to control levels despite further blood-pressure increases. Treatment did not affect plasma levels of catecholamines but did enhance pressor responsiveness to infused norepinephrine in some subjects. Hemodynamic studies indicated that hypertension in the recumbent position was related to increases in total peripheral-vascular resistance and not to changes in cardiac output. Clinically, hypertension in the recumbent position is an important risk of fludrocortisone treatment in patients with orthostatic hypotension. This unusual model of chronic mineralocorticoid-induced hypertension is not volume dependent but is related to increased peripheral-vascular resistance.

To assess the relationship of postural changes in blood pressure to risk of myocardial infarction, 1359 men were followed for an average of 8.7 years. The men were participants in the Normative Aging Study, a longitudinal study of aging initiated in 1963 at the Veterans Administration Outpatient Clinic in Boston. It was found that the relationship of sitting blood pressure to the subsequent incidence of myocardial infarction was modified by a variable formed by subtracting supine from standing diastolic blood pressure (L\DBP). The effect of sitting diastolic blood pressure on risk of myocardial infarction was confined primarily to men with a LADBP of 10 mm Hg or more. al measurements of blood pressure are predictive of subsequent coronary heart disease, predictability may be improved by considering pressure responses to certain stressful stimuli encountered during the day. One standardized stress stimulus is postural change, particularly the assumption of the standing position. The purpose of this study was to provide initial data concerning the relationship between postural changes in blood pressure and the incidence of myocardial infarction in a large cohort of men. MethodsThe population for this study was

We undertook this study to assess the frequency of renovascular hypertension in patients with azotemia and hypertension refractory to drug therapy and to determine the effects of renal revascularization on blood pressure and renal function in these subjects. Thirty-nine of 106 consecutive patients admitted for diagnostic evaluation of severe hypertension proved to have renovascular hypertension. Of 21 hypertensive patients with renal insufficiency, 10 appeared to have renovascular hypertension with either bilateral atherosclerotic renovascular disease or unilateral renal arterial stenosis in a solitary functioning kidney. Medical therapy in the hospital often induced further deterioration of renal function despite enhanced blood-pressure control. However, surgical revascularization or percutaneous transluminal angioplasty produced improvement or stabilization of renal function and control of blood pressure in all patients with azotemia who were treated in this manner, despite longstanding hypertension. The benefits of therapy have persisted for 10 to 42 months of follow-up. These studies indicate that refractory hypertension in association with renal insufficiency is a relatively common clinical presentation for renovascular hypertension and bilateral renal-artery disease. Diagnostic evaluation and consideration of renal revascularization appear warranted in such patients, both for the control of the hypertension and for improvement in renal function.

SUMMARY To assess the interaction between adrenergic activity and blood pressure regulation in patients with chronic renal failure, plasma norepinephrine (NE) and plasma renin activity (PRA) were measured before and after rigorous ultrafiltration. The significance of PRA was further assessed by anglotensin blockade with saralasin. Two patterns of response were defined: nine patients had low levels of PRA before and after hemodialysis. These patients showed a net fall in norepinephrine and no angiotensin dependence at any time. Failure to stimulate either PRA or norepinephrine was also observed during periods of marked hypotension. Seven other patients had higher PRA, which rose during bemodialysis. This was associated with an increase in NE and postdialysis angiotensin dependence. Patients experiencing hypotension in this group showed a sharp rise in NE, suggesting baroceptor-mediated adrenergic stimulation. In all patients sustaining hypotension during therapy, postdialysis PRA was closely correlated with NE. These results Indicate that hemodialysis mobilizes the renin-angiotensln system to maintain hypertension in a greater proportion of dialysis patients than previously supposed and that impaired renin release following hypotension may represent uremic autonomic dysfunction. (Hypertension 3: 294-299, 1981)