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Plasma renin activity does not predict the antihypertensive efficacy of chlorthalidone
A Salvetti1, R Pedrinelli, G Bartolomei
1Clinica Medica I, University of Pisa, Italy.
Insights
Renin-angiotensin II stimulation may impact how well diuretics lower blood pressure in hypertensive patients. However, individual renin activity levels do not reliably predict the best diuretic dose.
Area of Science:
- Cardiovascular medicine
- Pharmacology
- Nephrology
Background:
- Angiotensin II stimulation can limit diuretic effectiveness in hypertension.
- The role of renin-angiotensin II stimulation in the dose-response relationship of diuretics is not fully understood.
Purpose of the Study:
- To investigate if renin-angiotensin II stimulation causes the flat blood pressure dose-response relationship observed with diuretics.
- To determine if plasma renin activity can guide optimal diuretic dosing.
Main Methods:
- A double-blind, placebo-controlled, cross-over study involving 75 out-patients with essential hypertension.
- Treatment with chlorthalidone at doses of 12.5, 25, or 50 mg once daily for 3 weeks.
- Measurement of blood pressure and plasma renin activity.
Main Results:
- Chlorthalidone significantly reduced blood pressure, with a plateau effect observed at 25 mg once daily.
- Plasma renin activity increased with each chlorthalidone dose, showing a different trend than blood pressure response.
- Greater renin stimulation coincided with the plateau in blood pressure response, but no significant correlation was found between individual plasma renin activity and blood pressure changes.
Conclusions:
- Renin stimulation may influence the dose-hypotensive response relationship of diuretic agents in antihypertensive therapy.
- Measuring individual plasma renin activity is unlikely to be a useful guide for determining optimal diuretic dosage.
Abstract:
It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.