Endothelium-dependent and -independent relaxations to adenosine in guinea pig aorta.
Effects of endothelial removal and hypoxia on responses to adenosine, 5'-(N-ethylcarboxamido)-adenosine (NECA), 2-chloroadenosine, N6-cyclohexyladenosine (CHA), sodium nitroprusside, and acetylcholine were examined in guinea pig aortic rings. Rings contracted with 2 microM prostaglandin F2 alpha (PGF2 alpha) relaxed in a dose-dependent manner in response to all drugs. The order of potency of adenosine compounds was NECA greater than 2-chloroadenosine greater than adenosine greater than CHA. Endothelial rubbing potentiated the PGF2 alpha response by 11 +/- 3%, eliminated the acetylcholine (ACh) response, but had no effect on nitroprusside and CHA responses. Responses to adenosine, NECA, and 2-chloroadenosine were significantly depressed by rubbing (P less than 0.05). Oxyhemoglobin (5 microM) and metyrapone (0.1 mM) reduced ACh responses in intact rings but had no effect on the adenosine and nitroprusside responses. Indomethacin treatment (10 microM) did not alter ACh, nitroprusside, or adenosine responses in intact rings. Hypoxia (10% O2) potentiated maximal responses to adenosine (+26 +/- 3%) and nitroprusside (+28 +/- 4%) in intact and rubbed rings and reduced the maximal response to ACh in intact rings (-28 +/- 3%). It is concluded that 1) adenosine mediates relaxation in guinea pig aorta by endothelial-dependent and -independent mechanisms, 2) receptors involved in both endothelial-dependent and -independent relaxations are characteristic of the A2 adenosine subtype, 3) the endothelial response appears unrelated to EDRF or prostanoid release, and 4) the adenosine response is significantly potentiated by hypoxia.
Headrick
J P
JP
Department of Physiology, University of Virginia, Charlottesville 22908.
Berne
R M
RM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology*; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011466:Prostanoic Acids / Q000502:physiology
D011466:Prostanoic Acids; D009569:Nitric Oxide; D000241:Adenosine