Heterogeneity and underlying mechanism for inotropic action of endothelin‐1 in rat ventricular myocytes

Article date: April 1998

By: Hideki Katoh, Hajime Terada, Masaru Iimuro, Shiho Sugiyama, Ke Qing, Hiroshi Satoh, Hideharu Hayashi, in Volume 123, Issue 7, pages 1343-1350

To clarify the mechanisms underlying the positive inotropic action of endothelin‐1 (ET‐1), we investigated the effect of ET‐1 on twitch cell shortening and the Ca2+ transient in rat isolated ventricular myocytes loaded with a fluorescent Ca2+ indicator indo‐1.

There was a cell‐to‐cell heterogeneity in response to ET‐1. ET‐1 (100 nm) increased twitch cell shortening in only 6 of 14 cells (44 %) and the increase in twitch cell shortening was always accompanied by an increase in the amplitude of the Ca2+ transient.

The ETA‐ and ETB‐receptors antagonist TAK‐044 (100 nm) almost reversed both the ET‐1‐induced increases in twitch cell shortening and in the Ca2+ transient. In the ET‐1 non‐responding cells, the amplitude of the Ca2+ transient never increased.

Intracellular pH slightly increased (∼0.08 unit) after 30 min perfusion of ET‐1 in rat ventricular myocytes. However, ET‐1 did not change the myofilament responsiveness to Ca2+, which was assessed by (1) the relationship between the Ca2+ transient amplitude and twitch cell shortening, and by (2) the Ca2+ transient‐cell shortening phase plane diagram during negative staircase.

We concluded that there was a cell‐to‐cell heterogeneity in the positive inotropic effect of ET‐1, and that the ET‐receptor‐mediated positive inotropic effect was mainly due to an increase in the Ca2+ transient amplitude rather than to an increase in myofilament responsiveness to Ca2+.

To clarify the mechanisms underlying the positive inotropic action of endothelin‐1 (ET‐1), we investigated the effect of ET‐1 on twitch cell shortening and the Ca2+ transient in rat isolated ventricular myocytes loaded with a fluorescent Ca2+ indicator indo‐1.

There was a cell‐to‐cell heterogeneity in response to ET‐1. ET‐1 (100 nm) increased twitch cell shortening in only 6 of 14 cells (44 %) and the increase in twitch cell shortening was always accompanied by an increase in the amplitude of the Ca2+ transient.

The ETA‐ and ETB‐receptors antagonist TAK‐044 (100 nm) almost reversed both the ET‐1‐induced increases in twitch cell shortening and in the Ca2+ transient. In the ET‐1 non‐responding cells, the amplitude of the Ca2+ transient never increased.

Intracellular pH slightly increased (∼0.08 unit) after 30 min perfusion of ET‐1 in rat ventricular myocytes. However, ET‐1 did not change the myofilament responsiveness to Ca2+, which was assessed by (1) the relationship between the Ca2+ transient amplitude and twitch cell shortening, and by (2) the Ca2+ transient‐cell shortening phase plane diagram during negative staircase.

We concluded that there was a cell‐to‐cell heterogeneity in the positive inotropic effect of ET‐1, and that the ET‐receptor‐mediated positive inotropic effect was mainly due to an increase in the Ca2+ transient amplitude rather than to an increase in myofilament responsiveness to Ca2+.

British Journal of Pharmacology (1998) 123, 1343–1350; doi:10.1038/sj.bjp.0701743

DOI: 10.1038/sj.bjp.0701743

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