title: Prolonged blood pressure elevation following continuous infusion of angiotensin II-a baroreflex study in healthy humans.
abstract: ANG II interacts with the sympathetic nervous system at central nervous blood pressure-regulating structures, including the baroreflex. It is unknown whether prolonged BP elevation mediated by high ANG II plasma levels could induce a persistent shift of the central nervous baroreflex setpoint, lasting beyond the short ANG II plasmatic half time of a few seconds, thereby consolidating elevated BP and/or increased SNA in healthy humans. In a blinded crossover design, ANG II or placebo (saline) was infused for a 6-h period in 12 resting normotensive students (6 males, 6 females) raising BP to borderline hypertensive levels. Between 60 and 120 min after the infusion period, muscle sympathetic nerve activity (MSNA) was assessed microneurographically and correlated with oscillometric BP measurements and heart rate at supine rest (baseline) and during pharmacologic baroreceptor challenge. Infusion of ANG II increased BP to borderline-hypertensive levels, as intended, whereas heart rate remained unaltered. At baroreflex assessment (i.e., 60-120 min after end of infusion period), systolic BP was significantly higher compared with placebo (Δ8.4 ± 3.1 mmHg; P < 0.05), whereas diastolic values were nearly equal between conditions. Baseline MSNA was neither decreased nor increased, and baroreflex sensitivity to vasoactive drug challenge was not altered. Our results show that elevation of ANG II plasma levels over 6 h was able to increase systolic, but not diastolic, BP far beyond blood-mediated ANG II effects. MSNA or heart rate did not counter-regulate this BP elevation, indicating that ANG II had sustainably reset the central nervous BP threshold of sympathetic baroreflex function to accept elevated BP input signals without counter-regulatory response.
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; friedhelm.sayk@uksh.de.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Sayk
authors.affiliation: Institute of Radiology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; and.
authors.forename: Isabel
authors.initials: I
authors.lastname: Wobbe
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Twesten
authors.affiliation: Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;
authors.forename: Moritz
authors.initials: M
authors.lastname: Meusel
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Wellhöner
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;
authors.forename: Inge
authors.initials: I
authors.lastname: Derad
authors.affiliation: Department of Emergency Medicine, München-Bogenhausen Hospital, München, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Dodt
mesh_terms: D000222:Adaptation, Physiological; D000804:Angiotensin II / Q000008:administration & dosage* / Q000097:blood; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D016037:Single-Blind Method; D013997:Time Factors; D059289:Vascular Stiffness; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000097:blood; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II