Angiotensin II blockade during combined thiazide-beta-blocker treatment.
Sixteen patients (11 M, 5 F), median age 41 years, with essential hypertension insufficiently controlled on hydrochlorothiazide 75 mg/day (DBP greater than or equal to 100 mmHg) were investigated. Plasma renin concentration (PRC), angiotensin II concentration (PA II), aldosterone concentration (PAC), plasma noradrenaline concentration (PNAC), plasma volume (PV) and exchangeable sodium (NaE) were determined and a saralasin-infusion (5.4 nmol/kg/min) was carried out while the patients were on thiazide alone, and in fourteen cases, repeated 3 months later after addition of a beta-blocker (propranolol 6, metoprolol 6 and atenolol 2 patients). On thiazide alone PRC, PA II and PAC was higher than normal in the group as a whole and the angiotensin II-inhibitor, saralasin, caused a significant decrease in MAP in twelve out of sixteen patients. After addition of a beta-blocker SBP and DBP decreased from 164/109 mmHg to 136/94 mmHg. PRC and PA II decreased by 40% and 58%, respectively. At this point saralasin caused no significant change in MAP. No close correlation was found between changes in BP on beta-blocker treatment and either PRC, PA II or saralasin response on thiazide treatment. PV, NaE, PAC and PNAC did not change sigificantly. It is concluded that in pts with thiazide-induced stimulation of the renin-angiotensin system (RAS) addition of a beta-blocker leads to suppression of RAS and the angiotensin II dependence of the blood pressure is nearly abolished. This mechanism might well contribute to the antihypertensive effect of beta-blockade in this particular situation. However, the pharmacological changes induced by beta-blockade are very complex, and most likely other factors are involved in the antihypertensive effect of beta-blocking drugs.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010953:Plasma Volume; D012083:Renin / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology*; D012964:Sodium / Q000097:blood
D000319:Adrenergic beta-Antagonists; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D012504:Saralasin; D009638:Norepinephrine