Differential regulation of IGF-I, its receptor and GH receptor mRNAs in the right ventricle and caval vein in volume-loaded genetically hypertensive and normotensive rats

It has been suggested, mainly by in vitro findings, that cardiovascular tis sue in the spontaneously hypertensive rat (SHR) should be more prone to pro liferate/hypertrophy than that of the Wistar-Kyoto rat (WKY). The present s tudy tests the hypothesis that the tissue of the low-pressure compartment i n SHR, being structurally similar to that of the WKY, shows an increased gr owth response due to activation of the GH-IGF-I system. An aortocaval fistula (ACF) was induced in 64 SHR and WKY male rats and 44 rats served as controls. They were all followed for 1, 2, 4 and 7 days afte r surgery. In separate groups of SHR (n=4) and WKY (n=3), central venous pr essure was measured by telemetry recordings prior to opening of the fistula and for up to 16 h post-surgery. Systolic blood pressure was measured duri ng the week postsurgery. The right ventricular (RV) and the caval vein IGF- I mRNA and RV IGF-I receptor and GH receptor mRNAs were quantitated by mean s of solution hybridisation assay. In rats with ACF the systolic blood pressure decreased, approximately 29% i n SHII and 16% in WKY between 1 and 7 days post-surgery (P<0.05, n=5-6 in e ach group). SHR with ACF showed a transient elevation in central venous pre ssure vs WKY. Within the week following fistula induction both strains show ed a similar, pronounced increase in RV hypertrophy. SHR with ACF showed a smaller, or even blunted, overall response with respect to activation of th e GH-IGF-I system compared with WKY, the latter showing clear-cut elevation of gene expressions. Two days after shunt opening in SHR, RV and caval vei n IGF-I mRNA increased by 57% and 108% (P<0.05 for both, n=5-6 in each grou p) respectively, and these expressions were then turned off, whereas RV GH receptor and IGF-I receptor mRNA expression remained unaffected compared wi th WKY rats. WKY rats showed on average a later and a greater response of G H-IGF-I system mRNA expression vs SHR. The present in vivo study suggests that the SHR requires less activation of the GH-IGF-I system for creating a given adaptive structural growth respon se.