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The effect of labetalol on blood pressure, heart rate and the renin-angiotensin system was evaluated in 12 patients with severe essential hypertension (diastolic blood pressure greater than or equal to 120 mmHg, WHO: Phase I and II) who had been resistant to other therapeutic regimens. In 9 (76%) patients, labetalol produced a marked reduction in systolic and diastolic pressure (p less than 0.001), while the other 3 patients required the combination of high doses of the drug (1600 mg/day) with a diuretic to achieve normal blood pressure levels. The average dose which controlled blood pressure levels was 777 +/- 393 mg/day. Treatment produced a progressive decrease in heart rate. Side-effects were transient. In contrast to other beta-adrenergic blockers, treatment with labetalol did not modify plasma renin activity levels nor the total concentration of renin or inactive renin levels. During the 1-year follow-up none of the patients treated with labetalol developed cardiovascular accidents, while 4 cardiovascular events occurred in a group of 12 age-matched non-treated severely hypertensive patients. The results of this study indicate that labetalol, administered as a single therapy or in combination with a diuretic, can control blood pressure levels in severely hypertensive patients who had been resistant to the administration of other therapies. Its effects on blood pressure are not related to the renin-angiotensin system.

The effect of thyroid hormone on renin productiona and release by rat kidney slices was studied. Rat kidney slices were incubated in Warburg flasks containing Krebs-Ringer-Phosphate- Glucose- Dextran solution at 37 C for 5 hours. Renin content, renin released into the incubation media and oxygen consumption were measured. Kidney slices actively secreted renin. Kidney slices of hyperthyroid rats released more renin, and kidney slices of hypothyroid rats released less renin than normal kidneys (p less than 0.001). The addition of 1-thyroxine to the incubation medium increased significantly (p less than 0.001) renin release by kidney slices from normal and hypothyroid rats. Thyroid hormone affects renin release through a mechanism independent of the ouabain-sensitive sodium pump and protein synthesis, since ouabain and cycloheximide did not modify renin release or production. The results of this study suggest that thyroid hormone plays a role in renin release from the juxtaglomerular cells.

The effect of short-term (6 weeks) and long-term (7 years) guanfacine treatment on some metabolic and endocrine parameters was studied in patients with moderate hypertension. Short-term treatment decreased blood pressure and heart rate, and also produced a significant fall in urinary excretion of noradrenalin and prolactin. Long-term treatment, in addition, produced a progressive decrease in prolactin, total cholesterol and triglyceride levels, but did not change growth hormone levels and oral glucose tolerance test. The decreased mortality and morbidity which was observed under guanfacine treatment may depend not only on important antihypertensive activity of guanfacine, but also on its beneficial effect on known cardiovascular risk factors.

A comparative study of the effects of captopril, an angiotensin converting enzyme inhibitor and endralazine, a new vasodilator drug, were performed in a group of 20 homogeneous patients with moderate hypertension (WHO: phase I and II). Both drugs produced a marked (p less than 0.001) decrease in mean arterial pressure, but the drop in blood pressure levels and the percentage of patients free of side-effects (p less than 0.001) were greater in patients treated with endralazine. Neither drug affected the lipid profile, nor pulmonary function tests and both increased significantly (p less than 0.001) plasma renin activity levels. The results of this study suggest that both drugs may be recommended for the treatment of hypertensive asthmatic patients, but endralazine should be preferred as first-choice drug, due to its lower incidence of side-effects and higher hypotensive effect obtained with the administration of a lower daily dosage.