title: Modulation of sympathetic coronary vasoconstriction by cardiac renin-angiotensin system in human coronary heart disease.
abstract: BACKGROUND
  In humans, angiotensin II enhances the sympathetic coronary vasoconstriction elicited by the cold pressor test (CPT) and diving. Whether this enhancement depends on the circulating angiotensin II or on the locally produced angiotensin II is unknown, however.
  
  
  RESULTS
  We addressed this issue in 14 patients with severe coronary artery disease by evaluating the effects of a 2-minute CPT (n=14) and a 30-second dive (n=8) on mean arterial pressure (MAP, arterial catheter), heart rate (ECG), coronary sinus blood flow (CBF, thermodilution technique), and coronary vascular resistance (MAP/CBF ratio). The 2 stimuli were applied at the end of left intracoronary infusion of either saline or benazeprilat diluted at the concentration of 25 microgram/mL. The rate of benazeprilat infusion had been preliminarily demonstrated to reduce angiotensin II concentration in the coronary sinus without affecting its arterial concentration. The changes in MAP and heart rate induced by CPT and diving were superimposable during saline and benazeprilat infusions. The decrease in CBF induced by CPT and diving during saline infusion was changed into an increase during benazeprilat infusion with a significant attenuation of the coronary vasoconstrictor response.
  
  
  CONCLUSIONS
  In patients with coronary artery disease, an attenuation of sympathetic coronary vasoconstriction can be obtained by reducing cardiac angiotensin II formation without involving circulating angiotensin II. This suggests a role of the tissue renin-angiotensin system in modulating autonomic cardiac drive in humans.
authors.affiliation: Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Ospedale Maggiore IRCCS, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Saino
authors.forename: G
authors.initials: G
authors.lastname: Pomidossi
authors.forename: R
authors.initials: R
authors.lastname: Perondi
authors.forename: A
authors.initials: A
authors.lastname: Morganti
authors.forename: L
authors.initials: L
authors.lastname: Turolo
authors.forename: G
authors.initials: G
authors.lastname: Mancia
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001158:Arteries; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure; D003080:Cold Temperature; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000294:innervation* / Q000503:physiopathology*; D004242:Diving; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014661:Vasoconstriction
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000804:Angiotensin II; D012965:Sodium Chloride; C052133:benazeprilat