title: Angiotensin II blunts, while an angiotensin-converting enzyme inhibitor augments, reflex sympathetic inhibition in humans.
abstract: 1. The role of angiotensin (Ang)II in and the effects of angiotensin-converting enzyme (ACE) inhibitors on the regulation of sympathetic neural activity were examined in humans. 2. We measured baseline values of muscle sympathetic nerve activity (MSNA) and its reflex inhibition in 28 patients with essential hypertension with elevated plasma renin activity (PRA; > 1.0 ng/mL per h = 0.28 ng/L per s) before and after either acute or chronic oral administration of an ACE inhibitor or placebo and in 20 normotensive subjects before and after infusion of either AngII (5 ng/kg per min = 4.8 pmol/kg per min) or vehicle (5% dextrose). Muscle sympathetic nerve activity was recorded from the tibial nerve and its reflex inhibition was evaluated during pressor responses to bolus injection of phenylephrine (2 micrograms/kg, i.v.). 3. Blood pressure was significantly decreased (P < 0.01) after the acute oral administration of captopril (25 mg), accompanied by a slight increase in MSNA in patients with essential hypertension compared with control patients who received placebo administration. Reflex changes in MSNA were significantly augmented after oral administration of captopril (-4.1 +/- 0.5 vs -6.2 +/- 0.6%/mmHg, respectively; P < 0.01), with a significant reduction of plasma AngII, while they were not affected by placebo administration. 4. In contrast, acute AngII infusion was accompanied by decreases in both PRA and MSNA in normotensive subjects. Reflex changes in MSNA were significantly reduced after AngII infusion (-11.0 +/- 0.8 vs -7.4 +/- 1.0%/mmHg, respectively; P < 0.01) but not after vehicle alone. 5. Chronic ACE inhibition by 12 week oral imidapril administration (5-10 mg/day) significantly (P < 0.05) decreased baseline values of MSNA, which were accompanied by a significant (P < 0.05) increase in the reflex inhibition of MSNA, while plasma concentrations of noradrenaline were unaffected. 6. These results indicate that AngII blunts reflex inhibition of sympathetic neural activity and that inhibition of the renin-angiotensin system by an ACE inhibitor augments reflex regulation of sympathetic neural activity and reduces baseline values in patients with essential hypertension.
authors.affiliation: Second Department of Internal Medicine, Yokohama City University School of Medicine, Urafune Hospital, Japan. msna@urahp.yokohama-cu.ac.jp
authors.forename: E
authors.initials: E
authors.lastname: Miyajima
authors.forename: T
authors.initials: T
authors.lastname: Shigemasa
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: O
authors.initials: O
authors.lastname: Tochikubo
authors.forename: M
authors.initials: M
authors.lastname: Ishii
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D000804:Angiotensin II; D002216:Captopril; C065166:imidapril; D012083:Renin