title: Changes in the derived central pressure waveform and pulse pressure in response to angiotensin II and noradrenaline in man.
abstract: Peripheral pulse pressure provides a surrogate measure of arterial stiffness. Analysis of the central pressure waveform allows assessment of central pulse pressure and arterial stiffness. The aim of the present study was to assess the effect of vasoconstrictor drugs on pulse pressure amplification and arterial stiffness in vivo. Eight healthy male subjects (mean age 30 years) received an infusion of angiotensin II (1, 3, 6 and 10 ng kg(-1) min(-1)), noradrenaline (10, 30, 60 and 100 ng kg(-1) min(-1)) and matching placebo, in random order, on separate occasions. Peripheral blood pressure and cardiac index were recorded non-invasively. Pulse wave analysis was used to determine augmentation index (AIx), which provides a measure of systemic arterial stiffness, aortic stiffness and central arterial pressure. Infusion of both active drugs resulted in a significant increase in peripheral mean arterial pressure (PMAP), peripheral vascular resistance, AIx, aortic stiffness and central pulse pressure, but only angiotensin II reduced cardiac index. Peripheral pulse pressure was unaffected by infusion of angiotensin II but increased with noradrenaline, which also produced a greater reduction in pulse pressure amplification than angiotensin II. However, the linear relationship of PMAP with both AIx and aortic stiffness did not differ significantly between drugs. These results demonstrate that intravenous infusion of angiotensin II and noradrenaline increase aortic and systemic arterial stiffness. Despite a similar effect on both parameters, for a given change in PMAP, the two drugs had divergent effects on peripheral pulse pressure and pulse pressure amplification. These data reveal that assessment of peripheral pulse pressure does not always reliably predict changes in central pulse pressure or arterial stiffness.
authors.affiliation: Clinical Pharmacology Unit, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. ibw20@cam.ac.uk
authors.forename: I B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: H
authors.initials: H
authors.lastname: MacCallum
authors.forename: P C
authors.initials: PC
authors.lastname: Hupperetz
authors.forename: C J
authors.initials: CJ
authors.lastname: van Thoor
authors.forename: J R
authors.initials: JR
authors.lastname: Cockcroft
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003971:Diastole; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011674:Pulse; D012044:Regression Analysis; D013599:Systole
chemical_list: D000804:Angiotensin II; D004837:Epinephrine