Interaction of atriopeptin III and vasopressin on calcium kinetics and contraction of aortic smooth muscle cells.
The cellular mechanism of the vasodilatory action of atriopeptin III (APIII) on vasopressin (AVP)-induced Ca2+ mobilization and cell shape change in cultured vascular smooth muscle cells (VSMC) was studied. APIII (10(-8) M) attenuated the increase of intracellular free Ca2+, [Ca2+]i, induced by 10(-8) M AVP (234.0 +/- 14.8 vs. 310.0 +/- 28.4 nM, P less than 0.01). Similar results were obtained in 45Ca2+ efflux experiments. APIII (10(-7) M), however, did not alter AVP-induced inositol trisphosphate (IP3) production, although the levels of inositol-1-phosphate were significantly reduced. The effect of APIII to block or attenuate AVP-induced Ca2+ mobilization was associated with an inhibition of AVP-stimulated cell shape change. The effect of atrial natriuretic factor (ANF) on cell shape, however, occurred at lower ANF concentrations than the effect on the Ca2+ mobilization. APIII stimulated production of cyclic guanosine monophosphate (cGMP) in VSMC. The effect of APIII on AVP-stimulated Ca2+ mobilization was partially mimicked by the stable nucleotide 8-bromo cGMP and was not affected by the soluble guanylate cyclase inhibitor, methylene blue (10(-4) M). These results suggest that APIII exerts its vasodilatory effect, in part, by interference with vasopressor-stimulated Ca2+ mobilization in vascular smooth muscle cells, perhaps by stimulating particulate guanylate cyclase and cGMP. However, an effect of ANF on the contractile mechanism at a site independent of Ca2+ release is also suggested by the present results.
Meyer-Lehnert
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Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Caramelo
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Tsai
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Schrier
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D000818:Animals; D001013:Aorta, Thoracic; D001127:Arginine Vasopressin / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002132:Calcium Radioisotopes / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D007295:Inositol Phosphates / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008751:Methylene Blue; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007295:Inositol Phosphates; D009712:Nucleotides, Cyclic; D001127:Arginine Vasopressin; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D002118:Calcium; D008751:Methylene Blue