Extracellular Ca2+ dependence and diltiazem inhibition of contraction in rabbit conduit arteries and mesenteric resistance vessels.
The dependence of norepinephrine-(NE-) and high potassium (80 mM K) depolarization-induced contractions on extracellular versus intracellular calcium (Ca2+) pools was studied in strips of rabbit superior mesenteric artery and its branches, and in perfused mesenteric resistance vessels. 80 mM K contractions were abolished in the presence of 0 Ca2+ 2 mM EGTA in all arteries studied, whereas 10(-5) M NE-induced contractions and stimulated 45Ca efflux in 0 Ca2+ 2 mM EGTA decreased in a graded fashion from proximal to distal arteries. These data indicate a decreasing release of intracellular Ca2+ and an increasing dependence on extracellular Ca2+ for NE-induced contractions as one proceeds from proximal to distal arteries. This pattern was paralleled by increasing sensitivity of NE-induced contractions to inhibition by diltiazem (10(-9)-10(-4) M) from proximal to distal arteries, while inhibition of 80 mM K contractions was similar in all vessels. 45Ca influx induced by 10(-5) M NE in the resistance vessels, wherein the NE does not release intracellular Ca2+, is approximately 10,000-fold more sensitive to the action of diltiazem than that in the aorta. However, when the aorta is activated by 10(-8) M NE, it becomes more sensitive to inhibition by diltiazem than when it is activated by 10(-5) M NE. The former NE concentration does not release intracellular Ca2+ in the aorta, whereas the latter does. Thus, it appears that NE-induced 45Ca influx is most susceptible to inhibition by diltiazem when the NE has not also released intracellular Ca2+. We suggest that the release of intracellular Ca2+ by NE may make its stimulated Ca2+ influx less susceptible to inhibition by diltiazem.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; 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
D001552:Benzazepines; D004110:Diltiazem; D002118:Calcium; D009638:Norepinephrine