933-93 The Regression of Left Ventricular Myofibrillary Proteins by ACE-inhibition (Lisinopril) is Associated with an Increase in Protein Synthetic Rates in Vivo

Abstract

One of the most serious complications of systemic hypertension is myocardial tissue damage, including left ventricular hypertrophy, as a consequence of increased protein synthesis. However, the modulating role of translational events in the hypertrophy-regression transition is poorly understood, especially where therapeutic regimes have been employed. These events were investigated in vivo in a genetic model of hypertension, namely in the spontaneously hypertensive rat (SHR); comparative responses were investigated in normotensive Wistar Kyoto rats (WKY). Rats were used at 4 months of age and treated with either the ACE-inhibitor lisinopril (5 mg/kg/day) in tap water or plain tap water (controls). The groups were assigned as follows: WKY-CON, normotensive controls; WKY-LIS, normotensives plus lisinopril; SHR-CON, hypertensive controls; SHR-LIS, hypertensives plus lisinopril. Fractional rates of protein synthesis (k s defined as the percentage of the myofibrillary protein pool renewed each day; %/day) were measured in vivo with the flooding dose technique using L-[4 -3 H]phenylalanine. Left ventricular myofibrillary proteins were extracted by differential solubility and high-speed centrifugation techniques; purity was assessed with SDS-PAGE. After 8 weeks treatment the myofibrillary protein contents (mg per region) in normotensive rats were as follows (all data as mean ± SEMS, n = 6–9): WKY-CON, 45 ± 1 mg; WKY–LIS, 36 ± 1 (p < 0.001). In the hypertensive group regression of contractile protein content occurred; i.e., SHR-CON, 52 ± 3 mg; SHR-L1S, 38 ± 1 mg (p < 0.001). Corresponding k s values were: WKY-CON, 8.3 ± 0.2 %/d; WKY–LIS, 8.2 ± 0.3 %/d (NS). In the SHR-group k s values were: SHR-CON, 8.2 ± 0.3%/d; SHR-L1S, 9.2 ± 0.3 mg (p < 0.025) ACE-induced regression of contractile protein composition in hypertension is associated with an increase in rates of translation