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 rate (GFR) is well maintained in the spontaneously hypertensive rat (SHR). In old SHR, the RBF autoregulation is dependent upon prostaglandins as well as the sympathetic nervous system. The purpose of this study was to examine the role 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-Kyoto (WKY) rats using NO synthase (NOS) inhibition that has a minimal effect on the RBF. The autoregulation of RBF was examined using an adjustable aortic clamp above the renal arteries and an ultrasound Doppler flow probe on the left renal artery. The lower pressure limit of RBF autoregulation was examined before and after infusion of the NOS inhibitor N(G)-monometyl-L-arginine (L-NMMA; 500 microg. kg(-1).min(-1)). Separate groups were given a coinfusion of L-NMMA and L-arginine (5 mg.kg(-1).min(-1)) or Ringer solution. The autoregulation of the GFR was studied in continuously infused animals using the (125)I-iothalamate clearance. Measurements of the GFR were done at control blood pressure, at a renal arterial pressure 10 mmHg above the lower pressure 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 was maintained in all animals. The GFR was unchanged in all groups after infusion of L-NMMA, and the autoregulation of GFR was well maintained in all groups except in the 70-week-old SHR. In these animals, the fractional compensation of GFR decreased from 0.95 to approximately 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 this group. The results indicate that in hypertensive rats with renal hypertensive 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 autoregulation. As the GFR was unchanged during L-NMMA infusion, these observations suggest that postglomerular contraction during NOS inhibition may be involved in the regulation of GFR in 70-week-old SHR.
Kvam
F I
FI
Renal Research Group, Institute of Medicine, University of Bergen, Norway.
Ofstad
J
J
Iversen
B M
BM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase