CNP causes receptor-mediated positive dromotropic effects in anesthetized dog hearts.
No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not beta-adrenoceptor, in the dog heart.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
M
M
Hirose
Y
Y
Furukawa
Y
Y
Miyashita
F
F
Kurogouchi
K
K
Nakajima
M
M
Tsuboi
S
S
Chiba
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D006162:Guanylate Cyclase / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007267:Injections; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D020098:Natriuretic Peptide, C-Type; D010477:Perfusion; D011134:Polysaccharides / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
C072551:HS 142-1; D011134:Polysaccharides; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D011433:Propranolol; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D007548:Isosorbide Dinitrate