Clinical evaluation of a new antihypertensive vasodilating agent PR--G 138 Cl.

1 The cardiovascular effects of a new substance (PR--G 138) with vasodilating action were analysed in 12 patients with moderately severe essential hypertension on a 60 mEq sodium diet in a metabolic ward. To prevent tachycardia, propranolol 40 mg four times daily was given during the control period until blood pressure (BP) was stabilized, and continued throughout the study. 2 The compound was effective in every patient except one, who also was resistant to hydrallazine and diazoxide. Mean arterial pressure was lowered from a mean control value of 121 +/- 11 supine and 118 +/- 13 standing to 98 +/- 18 and 95+/- 15 mm Hg (P less than 0.001) respectively after a single oral dosage of 5 to 15 mg PR--G 138. The effect was maximal after 1--2 h and lasted up to 6 h. 3 With adequate dosage, there was no orthostatic reaction. Pulse rate and plasma renin activity did not rise during PR--G 138 treatment, and cardiac output increased only slightly, doubtlessly as a result of the propranolol therapy. In most patients 5 mg of the drug was sufficient to cause a drop of BP to normal levels. Exercise tolerance (bicycle ergometry) was constant or improved during drug action. One patient complained of headache, but no other side effects were seen provided that propranolol was taken when the drug was given. During 3 months treatments on an out-patient basis the effect was sustained in four of eight patients. No toxic effects have been noticed.