Mechanism of action of EDRF on pressurized arteries: effect on K+ conductance.
Experiments were performed to study the cellular mechanism of endothelium-derived relaxing factor (EDRF) on vascular smooth muscle. Rat femoral arteries were cannulated and pressurized to 100 mm Hg. Vascular smooth muscle membrane potential (Em) and diameter responses to perfusion with 5 x 10(-6) M acetylcholine (ACh) were measured in vessels precontracted with 5 x 10(-6) M norepinephrine (NE). Hyperpolarization (-35 +/- 1.2 to -66 +/- 2.0 mV) and dilation were observed during ACh administration. Both responses were abolished on removal of the endothelium with collagenase. A bioassay was developed in which two vessel segments from the same artery were connected in series. The downstream vessel was deendothelialized while the endothelium of the upstream vessel remained intact. The protocol used was the same as in the first set of measurements. Hyperpolarization and dilation were observed in both vessels during ACh perfusion. However, when the direction of the perfusate flow in the bioassay system was reversed so that the deendothelialized vessel was upstream, only the "endothelium-intact" vessel demonstrated vascular smooth muscle hyperpolarization. To examine the ionic mechanism underlying the hyperpolarization presumably by released EDRF, the Em was measured as a function of increasing extracellular potassium ([K+]o). In the presence of ACh (but not NE) the maximum depolarization produced by a decade increase of [K+]o (10-100 mM) was 50 mV. In the deendothelialized vessel, this depolarization was decreased significantly to 39 mV. Addition to the superfusate of 10 mM tetraethylammonium, a K+ channel blocker, significantly reduced the hyperpolarization caused by ACh-induced EDRF release.(ABSTRACT TRUNCATED AT 250 WORDS)
Kauser
K
K
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Stekiel
W J
WJ
Rubanyi
G
G
Harder
D R
DR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D004553:Electric Conductivity; D004594:Electrophysiology; D004730:Endothelium, Vascular; D005263:Femoral Artery / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology / Q000502:physiology*; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001685:Biological Factors; D013757:Tetraethylammonium Compounds; D009569:Nitric Oxide; D019789:Tetraethylammonium; D000109:Acetylcholine; D011188:Potassium