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 ki dney from a normotensive strain into a hypertensive strain was reported to decrease blood pressure. The enduring interpretation of these now classic e xperiments 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 gen otype of the donor kidney and not the genotype: of the recipient." Method's. To test the Dahl hypothesis, we determined the blood pressure eff ects of selective intrarenal versus extrarenal exchange of single chromosom e regions between the spontaneously hypertensive rat (SHR) and the normoten sive Brown Norway (BN) rat. Results. The replacement of a defined segment of chromosome 1 in the SHR wi th the corresponding chromosome region of the BN rat was sufficient to atte nuate hypertension when selectively achieved either inside the kidney or ou tside the kidney. Conclusions. The current finding (1) demonstrates that naturally occurring genetic variants exist that can regulate blood pressure when selectively ex pressed outside the kidney as well as inside the kidney, and (2) compels re consideration of the long-held view that in essential hypertension. the gen etic transmission of increased blood pressure is determined solely by the g enotype of the kidney.