Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia.
Hypoxia triggers a mechanism that induces vasodilation in the whole heart but not necessarily in isolated coronary arteries. We therefore studied the role of cardiomyocytes (CM), smooth muscle cells (SMC), and endothelial cells (EC) in coronary responses to hypoxia (PO(2) of 5-10 mmHg). In an attempt to determine the factor(s) released in response to hypoxia, we inhibited the contribution of adenosine, ATP-sensitive K(+) channels, prostaglandins, and nitric oxide. Isolated rat septal artery segments without (-T) and with a layer of cardiac tissue (+T) were mounted in a double wire myograph, and constriction was induced. Hypoxia induced a decrease in isometric force of 21% and 61% in -T and +T segments, respectively (P < 0.05). EC removal increased the relaxation to hypoxia in -T segments to 33% but had the same effect in +T segments (61%). Only one of the inhibitors, the adenosine antagonist in +T segments, partially affected the relaxation due to hypoxia. The role of adenosine is thus limited and other mechanisms have to contribute. We conclude that hypoxia induces a relaxation of SMC that is augmented by the presence of CM and blunted by the endothelium. A single mediator does not induce those effects.
Kerkhof
Cornel J M
CJ
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam 1081 BT, The Netherlands.
Van Der Linden
Peter J W
PJ
Sipkema
Pieter
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D019335:Nitroarginine; D016718:Arachidonic Acid; D000109:Acetylcholine; D005905:Glyburide; D007213:Indomethacin