Effect of AT1 Receptor Blockade on Expression of Genes for Type-1 Angiotensin II(AT1) Receptor Subtypes in Spontaneously Hypertensive Rats.

To elucidate the genetic alterations of gene expression and regulation of the type 1 angiotensin II receptor (AT1), we measured the relative levels of mRNAs of AT1A receptor and AT1B receptor subtypes in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The effect of treatment with a selective AT1 receptor antagonist, TCV-116 (1mg/kg/day for a week), on the levels of mRNAs of AT1 receptor subtypes was also studied. The relative levels of AT1A and AT1B receptor mRNAs in the adrenal gland, heart, aorta, and kidney were measured by a sensitive reverse transcriptase-polymerase chain reaction method. AT1A receptor mRNA was predominantly expressed in the heart and kidney, but AT1B receptor mRNA was dominant in the adrenal gland in both strains. AT1A and AT1B receptor mRNAs were equally expressed in the aorta. There were no significant differences between WKY and SHR in the levels of AT1A and AT1B receptor mRNAs except for aortic AT1B receptor mRNA, which was expressed less in SHR. There were no differences between WKY and SHR in the effect of an AT1 receptor antagonist, TCV-116, on the levels of AT1A and AT1B receptor mRNAs in those four organs. TCV-116 administration reduced the expression of AT1A receptor mRNA in the heart and aorta, and reduced the expression of AT1B receptor mRNA in the adrenal gland and heart. These results indicate that the expression of genes for AT1A and AT1B receptor subtypes is regulated in a tissue-specific manner in both strains. (Hypertens Res 1994; 17: 187-192)