Bromocriptine

The 1040 compounds used for the small molecule screen were from the Prestwick Chemical Library (Illkirch, France). The following compounds were obtained from Cayman Chemical (Ann Arbor, MI): TWS119 (#10011251), ipsapirone (#22075), bromocriptine (#14598), urapidil (#29004), trimipramine (#15921), dichlorphenamide (#23658), nimesulide (#70640), and mesalamine (#70265). Lithium chloride (LiCl) was obtained from Sigma (St. Louis, MO, #62476), lithium acetate was obtained from Aldrich Chemical Company (Milwaukee WI, #21,319–5), and bortezomib (BTZ) was obtained from EMD Millipore (#179324-69-7).

To generate mice with cardiomyocyte-specific deletion of PERK mice homozygous for the floxed PERK (The Jackson Laboratory, Bar Harbor, ME) were crossed with αMHC-Cre mice. Mice were maintained on a standard rodent chow diet with 12-h light and dark cycles. Mice were bred starting at the age of 8 weeks. Administration of bromocriptine (4 mg/kg/day, Cayman Chemical) was added in drinking water. For chronic (3 week) administration, osmotic minipumps (Alzet; LEP or PRL 400 iU/kg/day) were implanted in sedated nulliparous mice.
Transthoracic echocardiography was performed with a VEVO2100 (Visualsonics, Toronto, Canada) system in nonanesthetized mice. Parasternal short-axis projections were visualized and M-mode recordings at the mid-ventricular level were recorded. Heart rate, left ventricular (LV) end-systolic and end-diastolic dimensions were averaged from 5 beats. LV percentage of fractional shortening (FS) was then calculated %FS = 100 × (LVEDD–LVESD)/LVEDD. Systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were measured by tail-cuff plethysmography from Muromachi Kikai Co., Ltd. (Tokyo, Japan) before mice were killed. Rectal body temperature was measured by thermometer.