Differences in Ca2† Handling Along the Arterial Tree

Abstract

The effects of noradrenaline (NA) on rat, rabbit, and human mesenteric resistance vessels (MRVs) in Ca2+-free medium have been compared. The maximum tension obtained in the absence of extracellular Ca2+ is least and is lost most rapidly with time in the MRVs from rabbit, followed by those from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), Sprague-Dawley (SD) rats, and from humans. Hence, it seems that the utilization of intracellular Ca2+ during activation of human MRVs by NA may be more substantial than has been found in the animal models. Nonetheless, in studies of the effects of isradipine on NA-induced tension, the human MRVs are similarly sensitive to the effects of this Ca2+ antagonist as WKY rat MRVs have been shown to be. All these resistance vessels, therefore, present quite a contrast to large vessels from rabbit, such as aorta, wherein the utilization of intracellular Ca2+ for NA-induced contraction is far more substantial, and the sensitivity of NA-induced contractions to Ca2+ antagonists is orders of magnitude less than in the MRVs. The basis for high sensitivity of rat and rabbit MRVs to Ca2+ antagonists may lie, at least in part, in the fact that these vessels (from rabbit and rat) depolarize in response to NA from approximately -50 to -30 mV, while aorta (from rabbit) does not, and the affinities of Ca2+ antagonists for voltage-sensitive Ca2+ channels (VSCs) are known to be voltage-dependent. Finally, the effects of the putative K+ channel opener BRL 34915 in rat MRVs appear to involve two sites of action, one with a lower affinity (K1 approximately 0.1 microM), similar to that shown previously in rat aorta, and a second with a higher affinity (K1 approximately 0.01 nM). In summary, these studies provide further evidence that Ca2+ handling processes controlled by both intracellular organelles and by the plasma membrane differ in mesenteric resistance vessels from those in aorta and in other large arteries.