GENETIC SUSCEPTIBILITY TO HYPERTENSION-INDUCED RENAL DAMAGE IN THE RAT - EVIDENCE BASED ON KIDNEY-SPECIFIC GENOME TRANSFER

To test the hypothesis that genetic factors can determine susceptibili ty to hypertension-induced renal damage, we derived an experimental an imal model in which two genetically different yet histocompatible kidn eys are chronically and simultaneously exposed to the same blood press ure profile and metabolic environment within the same host. Kidneys fr om normotensive Brown Norway rats were transplanted into unilaterally nephrectomized spontaneously hypertensive rats (SHR-RT1.N strain) that harbor the major histocompatibility complex of the Brown Norway strai n. 25 d after the induction of severe hypertension with deoxycorticost erone acetate and salt, proteinuria, impaired glomerular filtration ra te, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SKR-RT1.N kidneys. Control experiments demonstrated that the strain differences in kidney damage could not be attributed to effects of transplantation-induced renal in jury, immunologic rejection phenomena, or preexisting strain differenc es in blood pressure. These studies (a) demonstrate that the kidney of the normotensive Brown Norway rat is inherently much more susceptible to hypertension-induced damage than is the kidney of the spontaneousl y hypertensive rat, and (b) establish the feasibility of using organ-s pecific genome transplants to map genes expressed in the kidney that d etermine susceptibility to hypertension-induced renal injury in the ra t.