Difference in susceptibility of developing renal damage in normotensive fawn-hooded (FHL) and August X Copenhagen Irish (ACI) rats after N-omega-nitro-L-arginine methyl ester induced hypertension

Previous studies using the fawn-hooded hypertensive (FHH) rat have indicated that genetic factors appear to be important in determining the susceptibility to develop renal damage. This was further investigated by comparing the effects of N-omega-nitro-L-arginine methyl ester (L-NAME) induced hypertension on functional and structural renal damage in two normotensive strains, the resistant August x Copenhagen Irish rat (ACI) and the normotensive fawn-hooded (FHL) rat, which also appears to carry a susceptibility locus for renal failure. Male rats were studied during chronic treatment with L-NAME in either a low dose (LD, 75 to 100 mg/L drinking fluid) or a high dose (HD, 175 to 250 mg/L). Survival of FHL rats was adversely affected by L-NAME treatment. All FHL-HD and 6 of 14 FHL-LD rats died before the end of the II weeks of follow-up, whereas all treated ACI rats except for one ACI-HD animal survived. In both strains, L-NAME caused a dose dependent increase in systolic blood pressure (SBP). However, at similar levels of SBP, the increase in albuminuria (UaV) was significantly higher in FHL compared with ACI, as was the incidence of glomerulosclerosis (GS). Both the SEP and the blood pressure burden (SBP-Av), defined as SEP averaged over the period of follow-up, directly correlated with UaV and GS in both strains. However, the increase in the degree of renal damage per millimeter of mercury increase in SEP or SBP-Av was significantly higher in the FHL than in the ACI rats. Our findings clearly show that FHL rats are more susceptible to developing renal damage after induction of hypertension by chronic L-NAME treatment. We conclude that there is an interaction between blood pressure and the genetic susceptibility to renal disease in the FHL rat. (C) 1997 American Journal of Hypertension, Ltd.