Role of nitric oxide in the autoregulation of renal blood flow and glomerular filtration rate in aging spontaneously hypertensive rats

Autoregulation of renal blood flow (RBF) and glomerular filtration rare (GF R) is well maintained in the spontaneously hypertensive rat (SHR). In old S HR, the RBF autoregulation is dependent upon prostaglandins as well as the sympathetic nervous system. The purpose of this study was to examine the ro le of nitric oxide (NO) in the autoregulation of RBF and GFR in aging SHR ( 70 weeks) as compared with young SHR (10 weeks) and age-matched Wistar-Kyot o (WKY) rats using NO synthase (NOS) inhibition that has a minimal effect o n the RBF. The autoregulation of RBF was examined using an adjustable aorti c clamp above the renal arteries and an ultrasound Doppler flow probe on th e left renal artery. The lower pressure limit of RBF autoregulation was exa mined before and after infusion of the NOS inhibitor N-G-monometyl-L-argini ne (L-NMMA; 500 mug.kg(-1).min(-1)). Separate groups were given a coinfusio n of L-NMMA and L-arginine (5 mg.kg(-1).min(-1)) or Ringer solution. The au toregulation of the GFR was studied in continuously infused animals using t he I-125-iothalamate clearance. Measurements of the GFR were done at contro l blood pressure, at a renal arterial pressure 10 mmHg above the lower pres sure limit of RBF autoregulation and at a renal arterial pressure of about 60-65 mmHg. In both SHR and WKY rats, infusion of L-NMMA increased the mean arterial blood pressure, and the RBF decreased in young SHR, while the RBF was unchanged in the WKY groups and aged SHR. The autoregulation of RBF wa s maintained in all animals. The GFR was unchanged in all groups after infu sion of L-NMMA, and the autoregulation of GFR was well maintained in all gr oups except in the 70-week-old SHR. In these animals, the fractional compen sation of GFR decreased from 0.95 to similar to 0 after infusion of L-NMMA, indicating that autoregulation of the GFR was lost during NOS inhibition. Coinfusion of L-NMMA and L-arginine normalized the GFR autoregulation in th is group. The results indicate that in hypertensive rats with renal hyperte nsive damage, the GFR autoregulation is strongly NO dependent, as doses of L-NMMA that do not interfere with the RBF have an effect on the GFR autoreg ulation. As the GFR was unchanged during L-NMMA infusion, these observation s suggest that postglomerular contraction during NOS inhibition may be invo lved in the regulation of GFR in 70-week-old SHR. Copyright (C) 2000 S. Kar ger AG. Basel.