Alicia Mattiazzi

Cecilia Mundiña-Weilenmann

Cornwell TL

Drago GA

Francis SH

Furakawa K

Furukawa K-I

Gladys Chiappe de Cingolani

Gustavo Rinaldi

Jiang H

Leticia Vittone

Levitsky DO

Lincoln TM

Lindemann JP

Lytton J

Matilde Said

Simmerman HKB

Susuki T

The contribution of endoplasmic reticulum (ER) and phosphorylation of phospholamban (PLB) to the relaxant effect of cGMP- and cAMP-elevating agents was studied in feline aorta. Sodium nitroprusside (NP, 100 μM) completely relaxed contracture induced by 10 μM norepinephrine. This NP-induced relaxation was partially prevented by tetraethylammonium, suggesting that a fraction of NP-induced relaxation was mediated by activation of K+channels. In the absence and presence of tetraethylammonium, the relaxant effect of NP was associated with a significant increase in Ser16phosphorylation of PLB immunodetected by phosphorylation site-specific antibodies. The relaxant effect of NP on aortic strips precontracted with 80 mM KCl was significantly reduced by 1 μM thapsigargin. This decrease, which represents the ER contribution to the relaxant effect of NP, reached 23 ± 9% at 100 μM NP and was closely associated with a dose-dependent increase in Ser16phosphorylation (128 ± 49% over control at 100 μM NP). Effects of NP were associated with a significant increase in activity of protein kinase G and were mimicked by 8-bromo-cGMP. Forskolin produced a dose-dependent relaxant effect on KCl-induced contracture, which reached 64 ± 8% at 50 μM and was associated with an increase in phosphorylation of Ser16residue of PLB (88 ± 18% over control). Thapsigargin reduced this relaxant effect by 38 ± 9%. 8-Bromo-cAMP mimicked effects of forskolin. The ER-mediated relaxant effect and the increase in Ser16phosphorylation produced by forskolin were partially blocked by the protein kinase A inhibitor H-89 (5 μM). The results indicate that ER partially contributes to the relaxant effect of NP and forskolin in feline aorta. This effect may be mediated by the associated increase in Ser16phosphorylation of PLB.</jats:p

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AJP Heart and Circulatory Physiology

Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta

Endoplasmic reticulum contribution to the relaxant  effect of cGMP- and cAMP-elevating agents in feline aorta

Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta

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