Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats.
The effects of nitric oxide synthase (NOS) inhibition (effected using L-NAME, 14 mg (kg body mass (BM))(-1), administered intravenously) on systemic and renal circulation and renal excretory function has been investigated in anaesthetized Wistar rats subjected to one of two different degrees of isotonic extracellular (EC) volume expansion (40 and 60 ml x kg(-1) (240 min)(-1)). The administration of L-NAME resulted in an increase in mean arterial blood pressure and total peripheral vascular resistance (TPR), and a significant reduction in cardiac output (CO) and the kidney fraction of CO in both experimental groups. The total renal blood flow (RBF) dropped from 557 + 43.4 to 149 +/- 13.1 ml x min(-1) (100 g BM)(-1) and from 592 +/- 45.9 to 191 +/- 16.3 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively. A redistribution of the intrarenal circulation from the medulla of the kidney toward the cortex may have occurred. The NOS inhibition induced a significant decrease in the glomerular filtration rate (GFR; from 1.18 +/- 0.10 to 0.53 +/- 0.08 ml x min(-1) (100 g BM)(-1) and from 1.26 +/- 0.07 to 0.73 +/- 0.08 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively), and the filtration fraction increased. The urine excretion dropped in parallel with the GFR, while the reduction in sodium and potassium excretion was more marked than that of the GFR, raising the possibility of a direct effect on the kidney tubules. The difference in EC volume expansion (the calculated increases in the EC volume in the last 90 min were 1.30 and 5.44% in the two time control groups and 3.66 and 7.45% in the two L-NAME-treated groups) did not induce any significant modification of the L-NAME effect.
Tost
H
H
Semmelweis University, Faculty of Medicine, Department of Physiology, Budapest, Hungary. tost@puskin.sote.hu
Hably
C
C
Lengyel
M
M
Gógl
A
A
Lendvai
A
A
Bartha
J
J
D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester