INSULIN-RECEPTOR EXON 11+ - ISOFORM MESSENGER-RNA IN SPONTANEOUSLY HYPERTENSIVE AND ADRENOCORTICOTROPIN-HYPERTENSIVE RATS/

Objective To test the hypothesis that insulin resistance of the sponta neously hypertensive rat (SHR) and adrenocorticotropin-hypertensive ra t is related to a difference in the proportion of the functionally dif ferent alternatively spliced exon 11 isoforms of the insulin receptor. Design We determined the proportions of mRNA for the exon 11+ and exo n 11- isoforms in various tissues of SHR and Wistar-Kyoto rats aged 3, 6, 9 and 12 weeks, which span the pre-hypertensive phase through to e stablished hypertension, as well as in Sprague-Dawley rats with adreno corticotropin-induced hypertension and Sprague-Dawley controls. Method s Detection of mRNA involved a reverse-transcriptase polymerase chain reaction technique specific for each isoform and quantification was by slot and dot blot hybridization. Results Mean proportions of exon 11 mRNA in SHR, Wistar-Kyoto rats, adrenocorticotropin-hypertensive rats and Sprague-Dawley control rats at each age were 95% for liver, 82% f or adipose tissue, 77% for kidney, 66% for adrenal, 53% for heart, 26% for cerebral cortex, 23% for hypothalamus, and 3% for skeletal muscle . There was also no difference in concentration of total insulin recep tor mRNA, Conclusions The absence of any difference in proportions of insulin receptor mRNA isoforms argues against the hypothesis that an a lteration of differential splicing plays a role in the models of hyper tension studied, I Hypertens 16:1009-1014 (C) 1998 Lippincott-Raven Pu blishers.