The significance of the endothelium for hypoxic vasodilatation.
In isolated segments of the A. carotis communis of the dog, the membrane potential and isometric tension were recorded in dependence on the oxygen partial pressure. In the range between 535 and 35 mmHg PO2, lowering of oxygen tension leads to a dose-dependent hyperpolarization of maximally 9.8 mV with a simultaneous decrease in tone of 0.746 g. Further reduction of PO2 below 35 mmHg causes depolarization and contraction. These effects can be abolished almost completely by alpha-receptor blockade. Application of 6-hydroxydopamine (1.8 mM) augments the hypoxic hyperpolarization and relaxation in the entire PO2 range between 535 and 0 mmHg, i.e., below 35 mmHg depolarization and contraction fail to appear. The increasing release of noradrenaline from terminal sympathetic nerve endings thus limits the hyperpolarization and relaxation occurring with reduction of PO2 and is mainly responsible for the depolarization and contraction below 35 mmHg. Application of indomethacin (10(-5) M) or BW 755 C (3.8 x 10(-5) M) reduces the hypoxic hyperpolarization and dilatation by circa 20-30%. Their maximum is shifted towards a higher PO2 of 65 mmHg. Only complete removal of the endothelium effects a 70-80% restriction of dilatory vascular reactivity. Identical quantitative statements hold also for control conditions, i.e. in carbogen Krebs solution. This means that the basal release of prostacyclin from endothelial and smooth muscle cells has a share of 20-30%, the basal release of the endothelial dilator EDHF of 70-80% in the membrane polarization and reduction in muscle tone.(ABSTRACT TRUNCATED AT 250 WORDS)
Siegel
G
G
Institute of Physiology, Free University of Berlin, FRG.
Grote
J
J
Schnalke
F
F
Zimmer
K
K
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D046508:Culture Techniques; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide