Angiotensin II blockade during combined thiazide-beta-adrenoreceptor-blocker treatment.
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.
D000328:Adult; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000097:blood; D001262:Atenolol / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D010953:Plasma Volume; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D012504:Saralasin; D012964:Sodium / Q000378:metabolism
D011412:Propanolamines; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D001262:Atenolol; D012964:Sodium; D011433:Propranolol; D012083:Renin; D008790:Metoprolol; D012504:Saralasin