Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat

The spontaneously hypertensive rat (SHR) develops much less renal damage than the stroke-prone strain of SHR (SHRsp) after salt-supplementation, and it has been proposed that these strains differ in their genetic susceptibility to renal damage. However, radiotelemetric BP measurements have shown that salt-supplementation results in more severe and accelerated hypertension in the SHRsp. Therefore, it is unclear whether the differences in renal damage are due to differences in BP exposure or true differences in intrinsic (genetic) renal susceptibility to hypertensive damage.

Kidney cross transplantation was performed between the SHR and SHRsp strains in uninephrectomized recipients to allow an investigation of the susceptibility to renal damage in SHR and SHRsp kidneys maintained in the same host and exposed to the same BP profile and metabolic environment. Following transplantation, BP was radiotelemetrically monitored before and after an 8% NaCl diet given to accelerate hypertension and renal damage. Then the kidneys were removed and renal damage was assessed histologically.

In the SHR recipients, the SHRsp donor kidneys exhibited more hypertensive damage than the contralateral native SHR kidneys, but histologic evidence of mild cellular immunologic rejection also was observed that could have facilitated the increased renal damage. However, even in SHRsp recipients, the native SHRsp kidneys exhibited twice the damage seen in the contralateral transplanted SHR kidneys.

These data unequivocally demonstrate that the SHRsp kidneys are intrinsically more susceptible than the SHR kidneys to renal damage when exposed to exactly the same BP and metabolic environment.