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Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent
Insights
E-643, an alpha-blocking agent, effectively lowered blood pressure in hypertensive patients across supine, sitting, and standing positions. While pulse rate increased in upright positions, plasma hormone levels remained unchanged.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Hypertension Research
Background:
- Essential hypertension remains a significant global health concern.
- Alpha-blocking agents are a class of drugs used to manage hypertension.
- Understanding the efficacy and side effect profile of new antihypertensive agents is crucial.
Purpose of the Study:
- To evaluate the blood pressure-lowering effects of E-643, a novel alpha-blocking agent, in patients with essential hypertension.
- To assess the impact of E-643 on blood pressure irrespective of patient posture (supine, sitting, standing).
- To investigate the influence of E-643 on plasma catecholamine and hormone levels.
Main Methods:
- A 7-day treatment study involving 15 inpatients (8 male, 7 female) with essential hypertension.
- Daily administration of 1 mg E-643, three times daily.
- Blood pressure and pulse rate measurements in supine, sitting, and standing positions.
- Plasma levels of noradrenaline, adrenaline, dopamine-beta-hydroxylase, renin, and aldosterone were measured before and after treatment.
Main Results:
- Significant reductions in systolic and diastolic blood pressure were observed in all measured positions (supine, sitting, standing).
- Pulse rate increased in sitting and standing positions but remained unaffected in the supine position.
- No significant changes were noted in plasma levels of adrenaline, noradrenaline, dopamine-beta-hydroxylase, renin, or aldosterone.
- Antihypertensive effects were more pronounced in patients with higher baseline plasma catecholamines and dopamine-beta-hydroxylase levels.
Conclusions:
- E-643 demonstrates significant antihypertensive efficacy across different postures in patients with essential hypertension.
- The drug's effect on blood pressure is not associated with significant alterations in key plasma hormone levels.
- While transient side effects like dizziness were reported, E-643 appears to be a promising agent for hypertension management.
Abstract:
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.