title: Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension.
abstract: BACKGROUND
  Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however.
  
  
  OBJECTIVE
  To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive.
  
  
  METHODS
  In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively.
  
  
  RESULTS
  Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.
authors.affiliation: Cattedra di Medicina Interna I, Ospedale S. Gerardo Monza, Università di Milano, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grassi
authors.forename: C
authors.initials: C
authors.lastname: Turri
authors.forename: R
authors.initials: R
authors.lastname: Dell'Oro
authors.forename: M L
authors.initials: ML
authors.lastname: Stella
authors.forename: G B
authors.initials: GB
authors.lastname: Bolla
authors.forename: G
authors.initials: G
authors.lastname: Mancia
mesh_terms: D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001775:Blood Circulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D017706:Lisinopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril