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It has been suggested, mainly by in vitro findings, that cardiovascular tissue in the spontaneously hypertensive rat (SHR) should be more prone to proliferate/hypertrophy than that of the Wistar-Kyoto rat (WKY). The present study tests the hypothesis that the tissue of the low-pressure compartment in SHR, being structurally similar to that of the WKY, shows an increased growth 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 after surgery. In separate groups of SHR (n=4) and WKY (n=3), central venous pressure was measured by telemetry recordings prior to opening of the fistula and for up to 16 h post-surgery. Systolic blood pressure was measured during the week post-surgery. The right ventricular (RV) and the caval vein IGF-I mRNA and RV IGF-I receptor and GH receptor mRNAs were quantitated by means of solution hybridisation assay. In rats with ACF the systolic blood pressure decreased, approximately 29% in SHR and 16% in WKY between 1 and 7 days post-surgery (P&lt;0.05, n=5-6 in each group). SHR with ACF showed a transient elevation in central venous pressure vs WKY. Within the week following fistula induction both strains showed a similar, pronounced increase in RV hypertrophy. SHR with ACF showed a smaller, or even blunted, overall response with respect to activation of the 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 vein IGF-I mRNA increased by 57% and 108% (P&lt;0.05 for both, n=5-6 in each group) respectively, and these expressions were then turned off, whereas RV GH receptor and IGF-I receptor mRNA expression remained unaffected compared with WKY rats. WKY rats showed on average a later and a greater response of GH-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 response.

journal of endocrinology/journal of endocrinology

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