Kidney-specific chromosome transfer in genetic hypertension: The Dahl hypothesis revisited

Background. A central dogma in the field of essential hypertension research is that the genetic transmission of increased blood pressure is determined solely by the genotype of the kidney. This concept is based in large part on studies in experimental rat models of spontaneous hypertension in which transplantation of a kidney from a hypertensive strain into a normotensive strain was reported to increase blood pressure, and transplantation of a kidney from a normotensive strain into a hypertensive strain was reported to decrease blood pressure. The enduring interpretation of these now classic experiments remains virtually unchanged from the view originally espoused a quarter century ago by Lewis Dahl, one of the founding fathers of the field of genetic hypertension research: "Blood pressure is determined by the genotype of the donor kidney and not the genotype: of the recipient." Method's. To test the Dahl hypothesis, we determined the blood pressure effects of selective intrarenal versus extrarenal exchange of single chromosome regions between the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN) rat. Results. The replacement of a defined segment of chromosome 1 in the SHR with the corresponding chromosome region of the BN rat was sufficient to attenuate hypertension when selectively achieved either inside the kidney or outside the kidney. Conclusions. The current finding (1) demonstrates that naturally occurring genetic variants exist that can regulate blood pressure when selectively expressed outside the kidney as well as inside the kidney, and (2) compels reconsideration of the long-held view that in essential hypertension. the genetic transmission of increased blood pressure is determined solely by the genotype of the kidney.