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

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 A 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 Ca2+. Contractile properties were evaluated using an lonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR90) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Intracellular Ca2+ properties were assessed by fura-2 and presented as Ca2+-induced Ca2+ release (CICR) and intracellular Ca2+-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, TR90, baseline intracellular Ca2+ level or intracellular Ca2+ decay. Elevation of extracellular Ca2+ 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.