title: C-type natriuretic peptide-mediated coronary vasodilation: role of the coronary nitric oxide and particulate guanylate cyclase systems.
abstract: OBJECTIVE
  We tested the hypothesis that C-type natriuretic peptide (CNP) mediates coronary vasodilation through activation of cyclic guanosine monophosphate (cGMP) by way of particulate guanylate cyclase.
  
  
  BACKGROUND
  CNP has known peripheral vasodilator properties, and preliminary data have suggested that it can function as a coronary vasodilator.
  
  
  METHODS
  The actions of CNP were studied in instrumented dogs and in organ chamber rings in the presence and absence of a known antagonist to particulate guanylate cyclase, HS-142-1. Additionally, the actions of HS-142-1 were tested on acetylcholine-mediated coronary vasodilation, and immunohistochemical staining was utilized to localize the presence of CNP in the coronary endothelium.
  
  
  RESULTS
  CNP relaxed isolated coronary arteries with (mean +/- SEM 45.9 +/- 7%*) and without (72.0 +/- 7%*) an endothelium (*p < 0.05 for CNP effect alone, p < 0.05 for endothelium vs. no endothelium with CNP). Intracoronary infusions increased coronary blood flow (baseline, 64.6 +/- 5.1 ml/min; CNP-5, 79.9 +/- 6.1*; CNP-20, 103.3 +/- 13.6* [*p < 0.05 vs. baseline value]) and reduced coronary vascular resistance (baseline, 1.6 +/- 0.3 mm Hg/ml per min; CNP-5, 1.4 +/- 0.3*; CNP-20, 1.2 +/- 0.3*). Intracoronary injections increased coronary blood flow (delta baseline coronary flow, 30 +/- 9* ml/min [*p < 0.05]). HS-142-1 significantly attenuated these increases (delta coronary flow, 30 +/- 9* ml/min [CNP] to 14 +/- 6 [CNP + HS-142-1] [p < 0.05 CNP vs. CNP + HS-142-1]) and the relaxation of organ chamber rings (56 +/- 7% [CNP] to 18 +/- 6% [HS-142-1 + CNP]). Finally, CNP was localized to the coronary endothelium and smooth muscle by immunohistochemical staining.
  
  
  CONCLUSIONS
  CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary vasodilation is attenuated by intracoronary HS-142-1. Intracoronary HS-142-1 does not affect acetylcholine-mediated coronary vasodilation. These observations support a role for exogenous CNP as a potent coronary vasodilator.
authors.affiliation: Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Wright
authors.forename: C M
authors.initials: CM
authors.lastname: Wei
authors.forename: C H
authors.initials: CH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: L L
authors.initials: LL
authors.lastname: Aarhus
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D006162:Guanylate Cyclase / Q000502:physiology*; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology; D011506:Proteins / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: C072551:HS 142-1; D011134:Polysaccharides; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase