Increased production of nitric oxide in coronary arteries during congestive heart failure.
Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.
O'Murchu
B
B
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Miller
V M
VM
Perrella
M A
MA
Burnett
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000097:blood; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D037342:Pertussis Toxin; D012016:Reference Values; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D019323:omega-N-Methylarginine
D001381:Azepines; D010566:Virulence Factors, Bordetella; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D000244:Adenosine Diphosphate; C024763:talipexole; D009320:Atrial Natriuretic Factor; D001120:Arginine; D015237:Dinoprost; D037342:Pertussis Toxin; D012083:Renin; D000109:Acetylcholine; D007213:Indomethacin