Iso-S-petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca2+ transients in adult rat ventricular myocytes.

Abstract

Petasites formosanus is an indigenous species of the medicinal plant Petasites which has been used to treat hypertension. Both S-petasin and its isoform iso-S-petasin have been shown to be the effective ingredients in P. formosanus. However, their effect on heart function has not been revealed. This study was to examine the effect of iso-S-petasin on cardiac contractile function at the myocyte level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz under 1.0 mM extracellular Ca(2+). Contractile properties were evaluated using an IonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR(90)) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Intracellular Ca(2+) properties were assessed by fura-2 and presented as Ca(2+)-induced Ca(2+) release (CICR) and intracellular Ca(2+) decay. Acute application of iso-S-petasin (10(-7) to 10(-4) M) elicited a concentration-dependent inhibition in PS and CICR, with maximal inhibitions of 51.0% and 31.0%, respectively. Iso-S-petasin also induced a concentration-dependent inhibition of+/-dL/dt without affecting TPS, TR(90), baseline intracellular Ca(2+) level or intracellular Ca(2+) decay. Elevation of extracellular Ca(2+) from 1.0 mM to 2.7 mM significantly antagonized the iso-S-petasin-induced depression in PS and CICR. These results demonstrated a direct depressant action of iso-S-petasin on ventricular contraction, which may work in concert with its antihypertensive action to reduce the cardiac load. The iso-S-petasin-induced decrease in CICR may play a role in its cardiac depressant effect.