INDUCTION OF GROWTH-HORMONE RECEPTOR AND INSULIN-LIKE GROWTH-FACTOR-IMESSENGER-RNA IN AORTA AND CAVAL VEIN DURING HEMODYNAMIC CHALLENGE

Induction of two-kidney, one clip hypertension (renal hypertension) is characterized by a slow increase in left ventricular tension and aort ic wall stress, as opposed to aortocaval fistula or shunt volume overl oad, which induces a marked and rapid onset of wall stress in the cava l vein and right ventricle. In the present study, we applied hemodynam ic challenge to study the growth response involving gene expression of insulin-like growth factor-I (IGF-I) and growth hormone receptor (GH- R) mRNA in aorta and caval vein. Volume overload and pressure overload were induced in Wistar rats by means of shunt and renal hypertension, respectively. Systolic pressure was measured before excision of the g reat vessels, which was performed between 2 and 12 days postoperativel y. Aortic and caval vein IGF-I and GH-R mRNA expressions were measured by means of a solution hybridization assay, and the caval vein was an alyzed for IGF-I protein by immunohistochemistry. In the volume-disten ded but not pressurized caval vein in shunt rats, verified by telemetr y recordings, there was an eightfold increase in IGF-I and 3.5-fold in crease in GH-R mRNA at day 4 versus control. The IGF-I protein appeare d to be localized in smooth muscle cells. In the aorta of the renal hy pertension group, changes were of a slower onset. At day 7, there was a fourfold increase in IGF-I and fivefold increase of GH-R mRNA expres sions versus sham-operated rats. Both the shunt caval vein and renal h ypertension aorta showed evidence of a structural adaptation of the gr owth response. The present study suggests that acute elevation in vasc ular wall stress is an important triggering factor for overexpression of IGF-I and GH-R mRNA in great vessels. The growth hormone/insulin-li ke growth factor axis may be an important link in mediating structural ly adaptive growth responses in the blood vessel wall.