Differences in norepinephrine activation and diltiazem inhibition of calcium channels in isolated rabbit aorta and mesenteric resistance vessels.
The mechanisms of norepinephrine stimulation of calcium ion entry in isolated rabbit aorta and mesenteric resistance vessels were studied through measurements of effects on calcium-45 influx, tension, and membrane potential. The resistance vessels were considerably less sensitive to norepinephrine than the aorta. The aorta exhibited complex dose-response curves for norepinephrine-stimulated calcium influx and contraction, whereas these were simple in the arterioles. Both vessels were depolarized with increasing concentrations of potassium. Norepinephrine did not depolarize the aorta, whereas it did depolarize the mesenteric resistance vessels. This result supports the contention that norepinephrine opens receptor-operated channels to induce calcium entry in the aorta, while it may activate potential sensitive calcium channels in the mesenteric resistance vessels. However, the maximum depolarization with norepinephrine (10(-4) M) in the arterioles was completely blocked by 10(-5) M diltiazem, whereas that induced by 80 mM potassium was unaltered by the diltiazem. Furthermore, 10(-4) M norepinephrine was able to stimulate virtually the same contraction and calcium influx in 80 mM potassium-depolarized arterioles as in normal polarized tissues. These results are consistent with norepinephrine opening of receptor-operated channels to allow calcium entry in the rabbit mesenteric resistance vessels. That the behavior of norepinephrine-activated channels in the aorta is more complex than in the arterioles is further illustrated by a dramatically decreasing sensitivity of norepinephrine-stimulated calcium influx to diltiazem with increasing norepinephrine in the aorta but not in the arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)
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C
Cauvin
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S
Lukeman
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J
Cameron
O
O
Hwang
C
C
van Breemen
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D007473:Ion Channels; D004110:Diltiazem; D002118:Calcium; D009638:Norepinephrine