Cyclooxygenase inhibition potentiates myogenic activity in skeletal muscle arterioles.
The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors.
Hill
M A
MA
Department of Medical Physiology, College of Medicine, Texas A&M University, College Station 77843.
Davis
M J
MJ
Meininger
G A
GA
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors; D006072:Gossypol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D024510:Muscle Development; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D016861:Cyclooxygenase Inhibitors; D009569:Nitric Oxide; D008528:Mefenamic Acid; D006072:Gossypol; D008751:Methylene Blue; D007213:Indomethacin