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REGULATION OF VASCULAR TONE BY ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR
Author(s) -
Cheung DW,
MacKay G Chen, MJ,
Burnette E
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03008.x
Subject(s) - hyperpolarization (physics) , pinacidil , depolarization , mesenteric arteries , membrane potential , cromakalim , endothelium derived hyperpolarizing factor , nitric oxide , chemistry , biophysics , contraction (grammar) , endothelium , vasodilation , medicine , anesthesia , anatomy , endocrinology , artery , resting potential , biochemistry , biology , stereochemistry , glibenclamide , agonist , receptor , nuclear magnetic resonance spectroscopy , diabetes mellitus
1. Endothelium‐derived hyperpolarizing factor (EDHF) mediates the nitric oxide (NO)‐independent component of the relaxation in rat mesenteric arteries. The relationship between hyperpolarization and vascular tone was studied by simultaneous recording of membrane potential with intracellular microelectrodes and tension in ring segments of rat mesenteric arteries. 2. By depolarizing arteries with high potassium solutions, it was determined that the threshold for contraction is approximately −46 mV. Maximum contraction was attained when the arteries were depolarized to −20 mV. Thus, 1 mV depolarization resulted in an approximate 4% increase in tone. This relationship was not altered in spontaneously hypertensive rats. 3. Noradrenaline (0.3 μmol/L) caused contraction and depolarized arteries by 13 mV. Acetylcholine caused endothelium‐dependent relaxation and hyperpolarization up to 14 mV. In the presence of N ω ‐nitro‐ L ‐arginine, the EDHF‐mediated relaxation was correlated to hyperpolarization. A hyperpolarization of 1 mV corresponded to a 4.3% decrease of the induced tone. 4. At concentrations (10 μmol/L) causing total relaxation, the maximum hyperpolarization induced by NO was only 7.6 mV. 5. A maximum relaxation of 88% was observed with pinacidil (3 μmol/L), despite a 25 mV hyperpolarization. Relaxations to NO and pinacidil were not correlated with hyperpolarization. At similar levels of hyperpolarization, NO and pinacidil elicited more relaxation than EDHF. 6. These studies show that vascular tone is very sensitive to membrane potential change in the range between −46 and −20 mV in the rat mesenteric artery. The relaxation response to EDHF, unlike that to NO and pinacidil, can be accounted for solely by its effect on the membrane potential.