Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS Rat

Objective Alterations in renal nitric oxide (NO) are involved in the hypert ension of the Dahl salt-sensitive (Dahl-SS) rat. We sought to identify the kinetics and sites of expression of the major NO synthase (NOS) isoforms. Design The renal expression of the major NOS were examined in Dahl-SS and s alt-resistant rats (Dahl-SR) while on a low salt (0.1% NaCl) diet at 3 and 9 weeks of age. Methods Renal biopsies from Dahl-SS and Dahl-SR rats were compared for evid ence of renal injury and for alterations in expression of the NOS enzymes b y quantitative immunohistochemistry. Results At 3 weeks of age Dahl-SS end Dahl-SR rats have normal renal histol ogy and similar immunohistochemical expression of NOS1, -2, and -3. At 9 we eks Dahl-SS rats had significantly higher blood pressure than Dahl-SR rats (P < 0.005), and lower macula densa NOS1 (P < 0.05) and cortical and medull ary NOS3 (P < 0.05). NOS2 was reduced in cortical tubules in biopsies showi ng severe tubulointerstitial damage, but was not significantly different be tween Dahl-SS and Dahl-SR groups as a whole. Dahl-SS rats also manifested g lomerular and tubulointerstitial injury. Tubular expression of osteopontin (OPN), which is an inhibitor of NOS2, correlated with the systolic BP in in dividual Dahl-SS rats (r(2) = 0.80, P < 0.0001). Conclusion Tubulointerstitial injury and the loss of NOS occur after birth and parallel the development of hypertension. We suggest that the structura l and functional changes that occur with renal injury in the Dahl-SS rat ma y contribute to the development of hypertension. J Hypertens 18:1497-1505 ( C) 2000 Lippincott Williams & Wilkins.