Differences in Ca2+ handling along the arterial tree: an update including studies in human mesenteric resistance vessels.
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.
Cauvin
C
C
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Weir
S W
SW
Bühler
F R
FR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism*; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D011758:Pyrroles; D019806:Cromakalim; D002118:Calcium; D009638:Norepinephrine