Characterization of the endothelium-derived hyperpolarizing factor (EDHF) response in the human interlobar artery.
BACKGROUND
In addition to nitric oxide (NO) and prostacyclin (PGI2), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present study was performed to determine the characteristics of the EDHF that mediates the NO/PGI2-independent hyperpolarization and relaxation of human renal interlobar arteries.


METHODS
Acetylcholine-induced, EDHF-mediated hyperpolarization and relaxation were assessed using sharp microelectrodes impaled into interlobar smooth muscle cells and in organ chamber experiments, respectively. All experiments were performed in the combined presence of NO synthase (NOS) and cyclooxygenase inhibitors and the thromboxane analog U46619.


RESULTS
Interlobar arteries demonstrated pronounced NO/PGI2-independent relaxations and hyperpolarizations that were sensitive to the blockade of calcium-activated K+-channels (KCa+ channels) by the combination of charybdotoxin and apamin and to the inhibition of the Na-K-ATPase by ouabain. Exogenously applied KCl also exhibited relaxations and hyperpolarizations that were sensitive to ouabain but insensitive to the combined inclusion of charybdotoxin and apamin. Relaxations induced by KCl were also observed in endothelium-denuded interlobar arteries.


CONCLUSIONS
These results indicate that in the human renal interlobar artery, EDHF-mediated responses display the pharmacologic characteristics of K+ ions released through endothelial KCa+ channels. Smooth muscle cell hyperpolarization and relaxation appear to be dependent on the activation of ouabain-sensitive subunits of the Na-K-ATPase.
Büssemaker
Eckhart
E
Institut für Kardiovaskuläre Physiologie, and Klinik für Urologie und Kinderurologie, Klinikum der J.W.G.-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Popp
Rüdiger
R
Binder
Jochen
J
Busse
Rudi
R
Fleming
Ingrid
I
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001685:Biological Factors / Q000502:physiology*; D065729:Cytochrome P-450 CYP2C9; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol; D006801:Humans; D009569:Nitric Oxide; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012077:Renal Artery / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013426:Sulfaphenazole / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001685:Biological Factors; D004791:Enzyme Inhibitors; C067410:endothelium-dependent hyperpolarization factor; D013426:Sulfaphenazole; D009569:Nitric Oxide; D010042:Ouabain; D011189:Potassium Chloride; D011464:Epoprostenol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000254:Sodium-Potassium-Exchanging ATPase