title: Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects.
abstract: Although beta-adrenergic-blocking drugs suppress the renin system (RAAS), plasma angiotensin II (Ang II) responses during beta-blockade have not been defined. This study quantifies the effects of beta-blockade on the RAAS and examines its impact on prorenin processing by measuring changes in the ratio of plasma renin activity (PRA) to total renin. In normotensive (N = 14) and hypertensive (N = 16) subjects, blood pressure (BP), heart rate, PRA, plasma prorenin, plasma total renin (prorenin + PRA), ratio of PRA to total renin (%PRA), plasma Ang II, and urinary aldosterone were measured before and after 1 week of beta-blockade. Plasma renin activity, Ang II, and urinary aldosterone levels were similar for normotensive and hypertensive subjects. Plasma renin activity correlated with Ang II. Total renin, which is proportional to (pro)renin gene expression, was lower in hypertensive subjects and was inversely related to BP. Beta-blockade decreased BP and heart rate in both groups, with medium- and high-renin hypertensive subjects responding more frequently than those with low renin. Beta-blockade consistently suppressed PRA, Ang II, and aldosterone. Total renin was unchanged, thus, %PRA fell. These results indicate that beta-blockers suppress plasma angiotensin II levels, in parallel with the marked reductions in PRA and urinary aldosterone levels in normotensive and hypertensive subjects. The suppression of Ang II levels was comparable to that produced during angiotensin converting enzyme (ACE) inhibition. However, by reducing prorenin processing to renin, beta-blockers do not stimulate renin secretion, unlike ACE inhibitors and Ang II receptor antagonists. This unique action of beta-blockers has important implications for the treatment of cardiovascular disease.
authors.affiliation: Department of Medicine, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York 10021, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Blumenfeld
authors.forename: J E
authors.initials: JE
authors.lastname: Sealey
authors.forename: S J
authors.initials: SJ
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Bragat
authors.forename: R
authors.initials: R
authors.lastname: Marion
authors.forename: M S
authors.initials: MS
authors.lastname: Pecker
authors.forename: J
authors.initials: J
authors.lastname: Sotelo
authors.forename: P
authors.initials: P
authors.lastname: August
authors.forename: T G
authors.initials: TG
authors.lastname: Pickering
authors.forename: J H
authors.initials: JH
authors.lastname: Laragh
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000652:urine; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004792:Enzyme Precursors / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects; D012083:Renin / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000319:Adrenergic beta-Antagonists; D000450:Aldosterone; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D004792:Enzyme Precursors; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000092502:Renin Inhibitors