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Angiotensin II blockade during combined thiazide-beta-adrenoreceptor-blocker treatment
Insights
Adding beta-blockers to hydrochlorothiazide lowers blood pressure by suppressing the renin-angiotensin system. This reduces angiotensin II (ANG II) dependence, improving hypertension control in patients with elevated renin activity.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Nephrology
Background:
- Essential hypertension is often inadequately controlled by monotherapy with diuretics like hydrochlorothiazide.
- The renin-angiotensin system (RAS) plays a crucial role in blood pressure regulation and can be activated by thiazide diuretics.
- Understanding the interplay between RAS activity and antihypertensive drug efficacy is vital for optimizing treatment strategies.
Purpose of the Study:
- To investigate the effect of adding beta-adrenoreceptor blockers to hydrochlorothiazide in patients with essential hypertension.
- To assess the impact of this combination therapy on plasma renin concentration, plasma angiotensin II concentration, and blood pressure.
- To determine the role of the renin-angiotensin system in mediating the antihypertensive effects of beta-blockers in this context.
Main Methods:
- Sixteen patients with essential hypertension uncontrolled by hydrochlorothiazide were studied.
- Measurements included plasma renin concentration, plasma angiotensin II concentration, plasma volume, and exchangeable sodium.
- A saralasin infusion was performed during thiazide monotherapy and after adding a beta-adrenoreceptor blocker (propranolol, metoprolol, or atenolol).
Main Results:
- On thiazide alone, saralasin significantly decreased blood pressure in 12/16 patients, correlating with plasma angiotensin II levels.
- The addition of beta-blockers reduced blood pressure from 164/109 mmHg to 136/94 mmHg and decreased plasma renin and angiotensin II by 40% and 58%, respectively.
- Following beta-blocker addition, saralasin no longer significantly altered blood pressure, indicating a loss of angiotensin II dependence.
Conclusions:
- In hypertensive patients with thiazide-induced RAS stimulation, beta-blockers suppress the renin-angiotensin system.
- This suppression leads to a disappearance of angiotensin II-dependent hypertension, contributing to the combination's antihypertensive effect.
- Beta-blocker addition effectively improves blood pressure control in patients whose hypertension is exacerbated by RAS activation from diuretics.
Abstract:
1. Sixteen patients (11 male, five female), median age 41 years, with essential hypertension insufficiently controlled by hydrochlorothiazide (75 mg/day; diastolic blood pressure greater than or equal to 100 mmHg), were studied. 2. Plasma renin concentration [renin], plasma angiotensin II concentration ([ANG II]), plasma volume and exchangeable sodium (NaE) were determined, and a saralasin infusion (5.4 nmol min-1 kg-1) was carried out while the patients were on thiazide alone and, in 14 cases, 3 months after addition of a beta-adrenoreceptor blocker (propranolol, six, metoprolol, six, and atenolol, two patients). 3. On thiazide alone, saralasin caused a significant decrease in mean arterial blood pressure in 12 out of 16 patients. The saralasin response was closely related to pre-saralasin plasma [ANG II] (r = 0.73, P less than 0.01). Plasma [renin] and [ANG II] were higher than normal in the group as a whole. 4. After addition of a beta-adrenoreceptor blocker systolic and diastolic blood pressure decreased from 164/109 mmHg to 136/94 mmHg. Plasma [renin] and [ANG II] decreased by 40 and 58% respectively. At this point, saralasin caused no significant change in mean arterial pressure. No close correlation was found between plasma [renin] or [ANG II] or saralasin response on thiazide treatment and changes in blood pressure during subsequent thiazide/beta-adrenoreceptor-blocker treatment. Plasma volume and NaE did not change significantly. 5. In patients with thiazide-induced stimulation of the renin-angiotensin system, addition of a beta-adrenoreceptor blocker leads to suppression of the system and, at the same time, ANG II-dependence of blood pressure disappears. This contributes to the antihypertensive effect of beta-adrenoreceptor blockers in this particular situation.