LEFT-VENTRICULAR INSULIN-LIKE GROWTH FACTOR-I INCREASES IN EARLY RENAL-HYPERTENSION

Increasing interest has been directed toward the possible role of trophically acting molecules as modulators or initiators, or both, of myocardial hypertrophy. The aim of the present study was to investigate the possible role of one such molecule, namely, insulin-like growth factor 1, in myocardial hypertrophy developed in response to renal artery stenosis. Two-kidney, one clip Goldblatt hypertension was induced in Wistar rats weighing 180 g, and sham-operated animals were used as controls. Blood pressure was increased as early as 2 days after clipping 133 +/- 4 versus 116 +/- 4 mm Hg, p < 0.05), and the increase persisted 4 and 7 days after clipping (148 +/- 6 versus 129 +/- 3 mm Hg, p < 0.01 and 171 +/- 5 versus 139 +/- 3 mm Hg, p < 0.01, respectively). Left ventricular weight followed a similar pattern (373 +/- 7 versus 350 +/- 8 mg, NS, 415 +/- 11 versus 386 +/- 9 mg, p < 0.01, and 466 +/- 11 versus 391 +/- 10 mg, p < 0.01 at 2, 4, and 7 days after clipping, respectively), but no changes in body weight between the groups were observed. Insulin-like growth factor I messenger RNA (mRNA) was quantified using a solution hybridization assay. After 4 days of renal hypertension, there was a significant increase in left ventricular insulin-like growth factor I mRNA (2.0 . 10(-18) +/- 0.48 . 10(-18) versus 0.4 . 10(-18) +/- 0.07 . 10(-18) mol . mu-g DNA-1), which was no longer detectable 7 days after clipping. When insulin-like growth factor I protein was visualized with immunohistochemistry, an enhanced abundance of the protein was demonstrated in the left ventricle 4 as well as 7 days after clipping, and the protein seemed mainly confined to the subendocardial layers where wall stress is highest. In the right ventricle, no changes in weight, insulin-like growth factor I mRNA, or protein could be detected. In conclusion, two-kidney, one clip Goldblatt hypertension induced an increase in insulin-like growth factor I mRNA as well as protein in the left but not in the right ventricle. The principal localization of the increase in insulin-like growth factor I to the subendocardial layers of the left ventricle suggests wall stress as the most probable initiating stimulus for the enhanced synthesis of insulin-like growth factor I.