Differential salt-sensitivity in the pathogenesis of renal damage in SHR and stroke prone SHR

The spontaneously hypertensive rat (SHR) and the stroke prone SHR (SHRsp) d isplay contrasting susceptibilities to the development of the severe hypert ensive lesions of malignant nephrosclerosis, both with aging and after the provision of a high salt intake on the background of a Japanese style "stro ke prone'' rodent diet. The SHR is relatively resistant, whereas the SHRsp is markedly susceptible. The responsible mechanisms remain controversial, B lood pressure (BP) radiotelemetry was used to investigate the interrelation ship between salt intake, systolic BP,;nd renal damage in 8- to 12-weck-old male SHR and SHRsp given a standard North American style diet for 6 weeks, a standard diet plus 1% NaCl as drinking water for 6 weeks, or an 8% NaCl diet plus tap water for 4 weeks. After 3 weeks, BP was significantly greate r in the SHRsp compared to the SHR and was significantly more sensitive to supplemental salt in the SHRsp than in SHR Average systolic pressures durin g week 5 (after 3 weeks on standard diet plus tap water, standard diet plus 1% NaCl, and 8% NaCl diet plus tap water) were 158.0 +/- 3.0 mm HE, 207.3 +/- 5.6 mm Hg, and 226 +/-: 9.4 mm Hg in SHRsp compared with 171.4 +/- 3.8 mm Hg, 180.6 +/- 3.8 mm Hg, and 190.3 +/- 5.0 mm Hg in SHR, In the absence of supplemental NaCl, both strains exhibited minimal evidence of hypertensi ve renal damage until about 16 weeks of age. A high salt intake resulted in the development of lesions of malignant nephrosclerosis (fibrinoid necrosi s and thrombosis of small vessels and glomeruli) in the SHRsp but not in th e SHR; semiquantitative histologic renal damage scores in SHRsp versus SHR being 10.4 +/- 2.0 versus 0.7 +/- 0.2 after 6 weeks of standard diet plus 1 % NaCl, and 32.1 +/- 2.5 versus 0.7 +/- 0.4 after 4 weeks of 8% NaCl diet plus tap water; P < .001 for both comparisons. The development of more seve re hypertension in salt-supplemented SHRsp could only partly account for th e severity of renal damage in SHRsp, the increase in which was disproportio nate to the increase in absolute BP. However, the rate of increase of BP wa s greater in the SHRsp and this might have contributed to the g greater ren al damage observed in the SHRsp. These data indicate that the contrasting g enetic susceptibility to renal damage between SHR and SHRsp is mediated, at least in part, by a differential BP salt sensitivity. <(c)> 2001 American Journal of Hypertension, Ltd.