P-325: Enhanced JNK2 activity in the hypertrophic heart ventricle of Prague-Hypertensive Rat (PHR) is independent of circulating or tissue endothelin (ET)

• Published in: American journal of hypertension Vol. 15; no. S3; p. 148A
• Main Authors: Kramer, Herbert J., Baecker, Angela, Bokemeyer, Dirk, Vogel, Volker, Heller, Jiri
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-04-2002
• Subjects: Cardiac Hypertrophie; Endothelin; MAP-Kinase
• DOI: 10.1016/S0895-7061(02)02676-6
• EISSN: 1941-7225; 1879-1905
• ISSN: 0895-7061

Since MAP kinases may be involved in cardiac hypertrophy in spontaneously hypertensive rats and their activation may be due to stimulation by ET, we studied MAP kinases ERK, JNK and p38 and gene expression of preproET-1 mRNA and of ECE-1 mRNA in atrial and ventricular tissues of PHR and their normotensive controls (PNR). Systolic blood pressure was 208±15 in PHR vs 121±5 mm Hg in PNR (p<0.01). Total heart weight was 316±4 in PHR vs 247±4 mg/100 g b.w. in PNR (p<0.01). Left and right ventricular weights were 168±4 (p<0.01) and 57±2 (n.s.) in PHR vs 121±5 and 53±3 mg/100 g b.w. in PNR. Western blot analysis and immunocomplex activity assay showed no differences in ERK or p38 MAP kinase but significantly greater phosphorylation of JNK2 in PHR than in PNR with an increase in JNK2 activity in left ventricle to 6.4±1.5 in PHR vs 2.5±0.5 O.D. in PNR (each n=5; p<0.05). Plasma ET-1,2 was 10.5±1.9 in PHR vs 12.3±1.3 fmol/ml in PNR (each n=12). Using competitive PCR for quantitative analysis preproET-1 mRNA in heart ventricle was 1.20±0.27 in PHR vs 1.10±0.22 fmol/mg RNAtotal in PNR. In atrial tissue it was 2.68±0.49 in PHR vs 2.91±1.04 fmol/mg RNAtotal in PNR (each n=5; n.s.). We found between PHR and PNR no differences in ECE-1 mRNA expression in heart ventricle (0.68±0.15 vs 0.64±0.11 fmol/mg RNAtotal) or in heart atrium (1.10±0.51 vs 1.11±0.38 fmol/mg RNAtotal). Similarly, no differences in cardiac ET-1 protein content were noted. Thus, despite marked cardiac hypertrophy atrial and ventricular preproET-1 mRNA and ECE-1 mRNA expression was similar in PHR and PNR suggesting that the rise in JNK2 activity, probably contributing to ventricular hypertrophy in this model of spontaneous hypertension, was independent of the circulating or local tissue ET-1 system.