Potassium channel activation, hyperpolarization, and vascular relaxation.
1) Numerous compounds and changes in physical state functions shift the membrane potential of vascular smooth muscle to more negative values. The consequence is a vasodilatation because Ca2+ channels are closed. K+ channel opening frequently causes the hyperpolarization. 2) Acidification of the blood substitute solution, a fall in O2 partial pressure, and an increase in blood flow dilate arterial vessels. Acidosis is associated with a rise in K+ permeability and a simultaneous fall in Na+ permeability. Prostacyclin has a 20-30% share, and EDHF a 70-80% share in hypoxic vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+ channel opening properties of this drug. A voltage-dependent K+ channel and a Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible for the hyperpolarization with iloprost and with oxygen deficiency. 3) With 23Na+ nuclear magnetic resonance techniques, it has been demonstrated that with flow-dependent vasodilatation, proteoheparan sulphate integrated in the membrane of endothelial cells possibly served as a "flow sensor". With an external strain, such a compound can go from a randomly coiled state to an oriented state. Based on these viscoelastic properties, heparan sulphate proteoglycan is present as a random coil under "no flow" conditions and as an unfurled filament structure with increasing flow. This conformational change produces additional anionic binding sites to which Na+ ions of the blood are bound. A membrane hyperpolarization could be directly initiated by this Na+ binding via the protein fraction within the macromolecule or via a change in zeta-potential. Therefore, these ions can trigger the signal transduction for a vasodilatory vessel reaction. Decrease in flow is followed by a structural change of the macromolecule towards coil conformation, a release of Na+ ions and, thus, an interruption of the signal chain. 4) Cicletanine, aqueous garlic extract, and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators. A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects. Under noradrenaline, the cicletanine effect is amplified. Aqueous garlic extract and ajoene exert a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 5) The stationary activation curve "developed force vs. membrane potential" satisfactorily explains the effects of K+ channel openers. The tight electromechanical coupling expressed by this curve comprises a 50% vasorelaxation for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling ratio is 5.1 mV/g.(ABSTRACT TRUNCATED AT 400 WORDS)
Siegel
G
G
Institute of Physiology, Free University of Berlin, FRG.
Walter
A
A
Schnalke
F
F
Schmidt
A
A
Buddecke
E
E
Loirand
G
G
Stock
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D046508:Culture Techniques; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D016285:Iloprost / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D004232:Diuretics; D015221:Potassium Channels; D011725:Pyridines; D015222:Sodium Channels; C038068:cicletanine; D019204:GTP-Binding Proteins; D016285:Iloprost; D002118:Calcium; D009638:Norepinephrine