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Systemic and renal hemodynamic effects of celiprolol in essential hypertensives
1Cattedra di Terapia Medica, University of Pisa, Italy.
Insights
Celiprolol effectively lowers blood pressure and heart rate in hypertensive patients by reducing norepinephrine levels. Its effects on renal hemodynamics and dopamine receptors were also investigated.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Essential hypertension management requires understanding drug mechanisms.
- Celiprolol's hemodynamic and humoral effects, particularly concerning dopamine receptors, warrant investigation.
Purpose of the Study:
- To evaluate celiprolol's systemic and renal hemodynamic effects.
- To assess if celiprolol's actions involve dopamine receptor activation.
- To examine celiprolol's impact on hormonal markers in hypertension.
Main Methods:
- Double-blind, randomized trial comparing celiprolol (400 mg/day) and placebo in 9 hypertensive patients.
- Measurements included blood pressure, heart rate, renal plasma flow, glomerular filtration rate, and plasma levels of renin, aldosterone, and norepinephrine.
- Effects were assessed with and without metoclopramide administration.
Main Results:
- Celiprolol significantly reduced mean blood pressure, heart rate, and plasma norepinephrine compared to placebo.
- Renovascular resistances decreased significantly despite unchanged renal plasma flow.
- No significant changes in glomerular filtration rate or plasma aldosterone were observed; renin activity showed a trend toward reduction.
Conclusions:
- Celiprolol demonstrates beneficial hemodynamic effects in hypertension, including reduced blood pressure and renovascular resistance.
- The reduction in norepinephrine appears to be a key mechanism, independent of dopamine receptor activation by metoclopramide.
- Celiprolol offers a promising therapeutic option for essential hypertension.
Abstract:
To evaluate the humoral and hemodynamic (both systemic and renal) effects of celiprolol and to assess whether these effects are at least partially due to the activation of dopamine (DA) receptors, 9 out-patients with mild to moderate uncomplicated essential hypertension, without any therapy for at least 3 weeks, received celiprolol (400 mg once daily) and placebo, each for 1 month, according to a double-blind randomized trial pattern. At the end of each treatment period, blood pressure, heart rate, renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and plasma norepinephrine were measured after administration of saline solution and intravenous metoclopramide. Compared with placebo, celiprolol significantly reduced mean blood pressure, heart rate and plasma norepinephrine. Plasma renin activity showed a tendency toward a reduction during celiprolol treatment, which was not associated with changes in plasma aldosterone. Despite the decrease in mean blood pressure, renal plasma flow did not change, so that renovascular resistances were significantly reduced. Glomerular filtration rate was unchanged and the filtration fraction showed a trend toward a reduction during celiprolol treatment. Percent decrements of renovascular resistances and of mean blood pressure induced by celiprolol tended to correlate with changes in plasma norepinephrine. Metoclopramide did not influence the hemodynamic (systemic and renal) effects of celiprolol nor plasma renin activity and plasma norepinephrine, and it increased aldosterone levels to a similar extent before and after administration of celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)