Effects of endothelin on sodium transport mechanisms: potential role in cellular Ca2+ mobilization.
The effects of endothelin on cellular Ca2+ mobilization were examined in cultured rat vascular smooth muscle cells (VSMC). Endothelin (10(-8)M) induced a rapid transient increase of [Ca2+]i from 77 +/- 3 to 104 +/- 5 nM (p less than .05) in VSMC. Preincubation (60 min) with endothelin (2 x 10(-6)M) increased basal [Ca2+]i from 77 +/- 3 to 105 +/- 8 nM (p less than .05). Preincubation with endothelin also enhanced vasopressin (10(-7)M)-stimulated peak levels of [Ca2+]i (528 +/- 20 nM vs 969 +/- 21 nM, p less than .01). Endothelin (10(-7)M) induced an intracellular alkalinization (7.18 +/- 0.03 vs 7.37 +/- 0.04, p less than .01) which was blocked by pretreatment with amiloride. The biphasic effects of endothelin on [Ca2+]i were similar to those of an endogenous inhibitor of Na-K-ATPase that we examined in a previous study. Therefore, we examined the effects of endothelin on Na-K-ATPase in an enzyme preparation from hog cerebral cortex. At high concentrations, endothelin (10(-5)M) inhibited Na-K-ATPase in vitro. Thus, endothelin may exert its vasoconstrictor effects at least in part via alterations of cellular Ca2+ mobilization in VSMC. While the rapid transient increase of [Ca2+]i appears to reflect intracellular Ca2+ mobilization, the sustained effect on [Ca2+]i may be related to an increase of intracellular sodium mediated by inhibition of Na-K-ATPase and/or more likely by stimulation of the Na+/H+-antiport.
Meyer-Lehnert
H
H
Medizinische Poliklinik, University of Bonn, West Germany.
Wanning
C
C
Predel
H G
HG
Bäcker
A
A
Stelkens
H
H
Kramer
H J
HJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D016232:Endothelins; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014662:Vasoconstrictor Agents
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium