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Hemodynamic effects of torcetrapib and cardiotonic steroids in rats
Author(s) -
Ma Xiuying,
Zhao Huawei,
Forrest Michael J.
Publication year - 2010
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.24.1_supplement.977.8
Subject(s) - aldosterone , medicine , ouabain , blood pressure , hemodynamics , bufalin , chemistry , endocrinology , apoptosis , biochemistry , organic chemistry , sodium
Torcetrapib (Pfizer), an inhibitor of cholesteryl ester transfer protein (CETP), increases blood pressure and aldosterone in humans and in animal models. We recently reported that torcetrapib‐induced increases in blood pressure are independent of circulating aldosterone but dependent on an intact adrenal‐cortex. In the present study, our goal was to explore whether other adrenal‐derived steroids or mediators, distinct from aldosterone, contribute to torcetrapib‐induced pressor effects in Sprague‐Dawley rats. The studies used conductance catheter technology and pharmacological tools. Initial studies, presented herein, have focused on cardiotonic steroids including ouabain and bufalin. Interestingly, the hemodynamic and pharmacologic profile of these compounds appears distinct from that of torcetrapib. Compared with vehicle, ouabain, bufalin, and torcetrapib increased systemic blood pressure, left ventricular pressure, and total peripheral resistance. However, ouabain and bufalin increased stroke volume and cardiac output whereas torcetrapib did not. In addition, the torcetrapib‐induced pressor effect was inhibited by the calcium channel blocker nifedipine whereas that of ouabain and bufalin was not. In conclusion: 1) these data suggest that the torcetrapib‐induced pressor effect is primarily due to an increase in total peripheral resistance but not cardiac output; 2) the hemodynamic response to torcetrapib is distinct from that of adrenal‐derived cardiotonic steroids.