Effects of endothelium on basal tone and agonist and O2 sensitivity in porcine coronary artery.
Paired rings of porcine left anterior descending artery, with and without endothelium as determined by thrombin-induced relaxation, were suspended for isometric force measurement in Krebs solution (95% O2-5% CO2). The response to 50 mM KCl was similar in both preparations, averaging 59.3 +/- 2.5 mN/mm2 (n = 28). In the absence of any treatment, de-endothelialized rings (-E) spontaneously contracted; i.e., a basal tone of 21.8 +/- 2.0% of the control 50 mM KCl contraction was measured against the base line after an N2-induced relaxation. Intact rings (+E) developed a basal tone of only 1.8 +/- 0.7% (n = 14). Upon decreasing PO2 in the bath from 95 to 20%, (approximately 665-140 Torr) -E showed a 12.9 +/- 2.8% increase in force compared with only 1.5 +/- 0.6% for +E (n = 10). Norepinephrine also preferentially constricted the -E rings (1 x 10(-6) M: -E = 13.6 +/- 2.0%, +E = 0.6 +/- 0.3%; 3 x -6 M: -E = 21.7 +/- 3.1%, +E = 3.3 +/- 1.1%, n = 8). A similar increase in sensitivity of the -E compared with the +E ring was observed for methoxamine, a nonmetabolized, alpha-1-selective agonist, KCl, Bay K 8644 and histamine, suggesting that the level of tone and not the endothelium per se underlies the changes in sensitivity. To test this hypothesis, the vasoconstrictive effects of decreasing PO2 and norepinephrine were also studied with tone altered by 10 mM KCl which increased the tone in both -E and +E.(ABSTRACT TRUNCATED AT 250 WORDS)
Ngai
J H
JH
Department of Physiology, College of Medicine, University of Cincinnati, Ohio.
Roth
P S
PS
Paul
R J
RJ
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D011433:Propranolol; D010100:Oxygen; D009638:Norepinephrine; D007213:Indomethacin