Cardiac remodeling and failure are regulated by a myriad of cardiac protein phosphorylations. In the present study, cardiac phosphoprotein patterns were examined in rodent and human hearts Left ventricular tissue samples were obtained from human systolic failing (n = 5) and control (n = 5) hearts and from two rat models of hypertensive heart failure, i. e., spontaneously hypertensive heart failure and Dahl salt-sensitive rats and corresponding controls. Phosphoproteins were separated by 2D-DIGE with Cydye staining, phosphoprotein patterns were analyzed using pixel intensity in rectified images. Specific phosphoproteins which were different in human versus rodent hearts were identified by MALDI-TOF/TOF Mass Spectrometry. Targeted pair-wise analyses showed differences (p < 0.05) in 26 % of the pixels, which included pixels containing phosphorylated troponin T, myosin light chain, peroxiredoxin, and haptoglobin. These results show differences in rodent versus human cardiac remodeling which will influence the translation rodent studies to humans in this area.

Meprins are neutral endopeptidases which belong to Astacin family of proteinases. Atrial natriuretic peptide (ANP) and bradykinin are preferred substrates. Meprin b is an integral membrane protein of brush border membranes of kidney tubule cells. Since ANP and bradykinin have been postulated to regulate the renal response to salt, we investigated the effect of salt on meprin in Sprague Dawley (SD) salt-resistant and Dahl salt-sensitive (SS) rats. Renal meprin b transcript abundance, measured by real-time reverse transcriptase/polymerase chain reaction (RT/PCR), was the same in Dahl SS and SD rats on 0.3% NaCl and SS rats on 8% NaCl, however, was 2-fold less (P 0.05) in SD rats on 8% NaCl. (n 10), suggesting that a decrease in meprin activity plays a mechanistic role in normal adaptation to a high salt diet. Thus, we investigated the effect of actinonin, an inhibitor of meprin activity, on blood pressure, measured by continuous radiotelemetry, in Dahl SS rats on an 8% NaCl diet. Actinonin (10mg/kg/IP) reduced mean arterial BP Hg (p 0.05, n 3) (see figure) The meprin gene was mapped, using a radiation-hybrid (RH) panel, to a reported quantitative loci (QTL) on chromosome 18 for blood pressure in the Dahl SS rat. Together, this data suggests that renal meprin plays a mechanistic role in normal salt-adaptation; is a good candidate gene for hypertension in the Dahl rat; and a novel therapeutic target for hypertension.

Am J Hypertens (2004) 17, 90A–90A; doi: 10.1016/j.amjhyper.2004.03.229

Am J Hypertens (2004) 17, 140A–140A; doi: 10.1016/j.amjhyper.2004.03.369