Endothelium-dependent contraction and relaxation of the human and canine internal mammary artery: studies on bypass graft vasospasm.
The internal mammary artery (IMA) is the preferred conduit for coronary artery bypass graft because of superior late patency. However, IMA vasospasm may contribute to myocardial ischemia and early postoperative morbidity. To investigate mechanisms of vasospasm, we compared the reactivity of human and canine IMA segments in vitro to agonists known to release endothelium-derived contracting factor and endothelium-derived relaxing factor. Rings (4 mm in length) of human and canine IMA were studied in organ chambers. Human and canine vascular smooth muscle exhibited comparable contraction to norepinephrine (maximum = 7.55 +/- 0.63 gm and 6.4 +/- 0.90 gm, respectively) and relaxation to sodium nitroprusside. Human and canine IMAs exhibited comparable endothelium-derived relaxing factor-mediated relaxations to acetylcholine (human) and methacholine (canine). Human and canine IMA also exhibited comparable endothelium-dependent contraction to hypoxia (to 173.3% +/- 8.1% and 178.9% +/- 16.0% of initial prehypoxic tension; means +/- SEM; n = 12). Endothelium-dependent contraction to hypoxia in human and canine IMA could be attenuated by NG-monomethyl-L-arginine (10(-6) mol/L), a competitive inhibitor of L-arginine metabolism (n = 9 and n = 10 for human and canine; p less than 0.05). These studies establish that the canine is an appropriate model for study of human IMA vascular reactivity and that hypoxia can induce the release of an L-arginine-dependent, endothelium-derived contracting factor in the human and canine IMA. In vivo, the release of endothelium-derived contracting factor in response to hypoxemia may be cause of IMA vasospasm.
Lin
P J
PJ
Section of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905.
Pearson
P J
PJ
Schaff
H V
HV
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000502:physiology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016232:Endothelins; D016210:Methacholine Chloride; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine