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 susceptibility to hypertension-induced renal damage, we derived an experimental animal model in which two genetically different yet histocompatible kidneys are chronically and simultaneously exposed to the same blood pressure profile and metabolic environment within the same host. Kidneys from 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 strain. 25 d after the induction of severe hypertension with deoxycorticosterone acetate and salt, proteinuria, impaired glomerular filtration rate, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SHR-RT1.N kidneys. Control experiments demonstrated that the strain differences in kidney damage could not be attributed to effects of transplantation-induced renal injury, immunologic rejection phenomena, or preexisting strain differences 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 spontaneously hypertensive rat, and (b) establish the feasibility of using organ-specific genome transplants to map genes expressed in the kidney that determine susceptibility to hypertension-induced renal injury in the rat.
Churchill
P C
PC
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. pchrchl@med.wayne.edu
Churchill
M C
MC
Bidani
A K
AK
Griffin
K A
KA
Picken
M
M
Pravenec
M
M
Kren
V
V
St Lezin
E
E
Wang
J M
JM
Wang
N
N
Kurtz
T W
TW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000235:genetics*; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics*; D016030:Kidney Transplantation; D009400:Nephrosclerosis / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D003900:Desoxycorticosterone