Role of the endothelium and arginine peptides on the vaso-motor response of porcine internal mammary artery.
The long-term patency of the internal mammary artery (IMA) graft is of considerable interest owing to its extensive use in myocardial revascularization. The aim of the present study was to elucidate the role of endothelium in modulating the responses of the porcine IMA to several vasoactive drugs. Isolated ring segments of porcine IMA contracted in a reproducible and dose dependent manner to phenylephrine, potassium chloride and the thromboxane mimic U46619, but the responses to serotonin, histamine and ATP were significantly less prominent. Both acetylcholine and bradykinin elicited endothelium-dependent relaxation which was not inhibited by indomethacin, but by methylene blue, an inhibitor of soluble guanylate cyclase. These two endothelium-dependent drugs and two endothelium-independent relaxing drugs, nitroprusside and nitroglycerin relaxed the IMA in a dose dependent manner which was associated with an elevation of cyclic GMP. The endothelium dependent vasodilator peptides such as bradykinin contain L-arginine in their sequence. Benzoyl derivatives of L-arginine but not L-arginine relaxed the IMA in a dose dependent manner. These data confirm and extend exploratory studies performed with a simpler vascular model which indicate that the precursor of endothelium derived relaxing factor (EDRF) is an arginine moiety.
Thomas
G
G
Department of Physiology and Biophysics, Georgetown University Medical Center, NW Washington, DC 20007.
Vargas
R
R
Wroblewska
B
B
Ramwell
P W
PW
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D008323:Mammary Arteries / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D013552:Swine; D013895:Thoracic Arteries / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001120:Arginine; D006152:Cyclic GMP