Objective: To test the hypothesis that insulin resistance of the spontaneously hypertensive rat (SHR) and adrenocorticotropin-hypertensive rat is related to a difference in the proportion of the functionally different, alternatively spliced exon 11 isoforms of the insulin receptor.
Design: We determined the proportions of mRNA for the exon 11+ and exon 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 established hypertension, as well as in Sprague-Dawley rats with adrenocorticotropin-induced hypertension and Sprague-Dawley controls.
Methods: 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% for 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 receptor mRNA.
Conclusions: The absence of any difference in proportions of insulin receptor mRNA isoforms argues against the hypothesis that an alteration of differential splicing plays a role in the models of hypertension studied.