Early effects of tetraethylammonium chloride on the contractile properties of isolated rabbit basilar arteries.
The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries. Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE). The greater magnitude of the contractions was of the following order: [K+] greater than 5-HT greater than TEA greater than NE. High concentrations of TEA alone (10(-2) M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent. Low concentrations of TEA (10(-8)-10(-6) M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10(-7) M) and NE (3 X 10(-6) M) and attenuated the contraction produced by 60 mM [K+]. An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10(-2) M), but not high [K+], the subsequent addition of 5-HT (10(-7) M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10(-8) or 10(-6) M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10(-4) M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10(-3) M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 +/- 9% and 149 +/- 14% of control values following the second and third applications, respectively). With TEA (10(-6) M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10(-2) M) or [K+] (60 mM) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10(-5) M) were less sensitive to withdrawal of calcium from the extracellular medium (31 +/- 6% relative to the maximal response at 4 mM calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity.
D000818:Animals; D001488:Basilar Artery; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D007473:Ion Channels / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D019789:Tetraethylammonium; D009638:Norepinephrine