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Withapysalin induced cardiac positive inotropism: in vitro and in vivo studies
Author(s) -
Nascimento NIlberto R,
Amorim Luciana Siqueira,
Gomes Victor M,
Santos Claudia F,
Fonteles Manasses C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.879.5
Subject(s) - chronotropic , inotrope , propranolol , in vivo , atrium (architecture) , medicine , chemistry , guinea pig , endocrinology , heart rate , blood pressure , biology , atrial fibrillation , microbiology and biotechnology
The cardiac effects of Withapysalin F, isolated from Acnistus arborescens were evaluated in vivo and in vitro . Guinea pigs were infused with Withapysalin F (25 and 50 μg/Kg/min) and them evaluated parameters such as maximum intraventricular pressure, heart rate, dP/dt maximum, dP/dT minimum and tau, comparing to control and isoproterenol (1 μg bolus). Withaphysalin F increased maximal intraventricular pressure and dP/dt, while there was no significant change in frequency, minimum dP/dT and tau. In vitro assays, concentration‐response curves (0.2 to 145 μM) were made in spontaneous beating right atrium as left stimulated electrically atrium. Withapysalin F increased force in the right atrium by 250 ± 50%, without chronotropic effect. Withapysalin F increased tension by 338.75 ± 21.55% in the left atria. Propranolol (1μM), did not inhibit the positive inotropism. No changes in cAMP levels were detected. Furthermore, pretreatment with H89 (10 μM), a PKA inhibitor, did not decrease Withaphysalin F positive inotropic effect in guinea pig left atrium. However, incubation of ruthenium red (70 μM) abolished the positive inotropism promoted by Withaphysalin F. Withaphysalin F inotropic activity appears to be dependent on the activity of RYR2 receptors regardless of increase of cAMP and activation of PKA. This project was approved by the ethics committee with the protocol number: 12235749–3. Financial Support: FUNCAP