Objective: A pathogenetic role of altered alpha 2-adrenoceptors in essential hypertension has been suggested, based on studies in humans and animals. To examine the role of the alpha 2-adrenoceptor in genetically hypertensive rats, we compared the alpha 2-adrenoceptor genes of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats by restriction fragment length polymorphism analysis using human alpha 2-adrenoceptor probes (alpha 2-C10) and Dde I restriction endonuclease, and conducted a genetic cosegregation study.
Method: Five female WKY rats were bred with five male SHRSP. Eight pairs of F1 rats were mated in brother-sister pairs to yield an F2 population of 84 rats. Systolic blood pressure was determined by tail-cuff sphygmomanometry. Direct arterial blood pressure was taken under ether anaesthesia just before the rats were killed. Southern blots were performed using alpha 2C10 as a probe and the DNA from the F2 generation.
Results: A restriction fragment length polymorphism of the SHRSP allele of a 1.6-kb fragment and a WKY rat allele of a 0.9-kb fragment with a common band of 1.3 kb in SHRSP and WKY rats was found, as reported previously. The distribution of the genotype based on restriction fragment length polymorphism conformed to a 1:2:1 ratio in F2 rats, as expected for a Mendelian trait. There was no significant difference in the blood pressure of F2 rats with respect to alpha 2-adrenoceptor genotype.
Conclusion: This study demonstrated that the alpha 2-adrenoceptor gene restriction fragment length polymorphism distribution is a Mendelian trait in the F2 rats of crossed SHRSP and WKY rats, but failed to show genetic cosegregation of this restriction fragment length polymorphism with blood pressure in this generation.