Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent.
To determine whether E-643, a new alpha-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37--73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-beta-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172 +/- 31/100 +/- 12 leads to 151 +/- 28/89 +/- 14 mmHg), sitting (158 +/- 22/101 +/- 11 leads to 138 +/- 28/89 +/- 15 mmHg) and standing (153 +/- 32/103 +/- 21 leads to 129 +/- 31/89 +/- 20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67 +/- 10 leads to 69 +/- 10 beats/min), but was increased in the sitting (68 +/- 10 leads to 73 +/- 9 beats/min) and standing (73 +/- 10 leads to 81 +/- 11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-beta-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-beta-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D004299:Dopamine beta-Hydroxylase / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D011674:Pulse / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D012083:Renin / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D000450:Aldosterone; C018176:bunazosin; D004299:Dopamine beta-Hydroxylase; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine