Basal nitric oxide synthase activity is a major determinant of glomerular haemodynamics in humans.
BACKGROUND
Experimental data suggest that increased nitric oxide synthase (NOS) activity contributes to preglomerular vasodilation and subsequent glomerular hyperfiltration. Whether such a relationship also exists in the human renal vasculature has not yet been adequately determined.


RESULTS
We assessed systemic, renal, and intragomerular haemodynamics in 310 subjects with normal renal function [glomerular filtration rate (GFR) > 60 ml/min per 1.73 m], before and after NOS inhibition with L-Nmonomethyl arginine (L-NMMA). Subjects were arbitrarily divided into tertiles according to their basal NOS activity, as assessed by the decrease in renal plasma flow in response to L-NMMA (high -23.4 +/- 8.1 versus medium -10.8 +/- 2.2 versus low -1.0 +/- 4.8%). Resting GFR differed significantly between tertiles: high 114 +/- 21 versus medium 109 +/- 19 versus low 104 +/- 21 ml/min per 1.73 m; analysis of variance P = 0.003. In a multiple stepwise regression analysis, basal NOS activity was the major factor to explain resting GFR (beta = -0.344; P < 0.001). Body weight (beta = -0.295; P < 0.001) and age (beta = -0.164; P < 0.001) emerged as additional factors, whereas body mass index and blood pressure did not enter the final model. The close relationship between resting GFR and basal NOS activity was also mirrored in the renal microcirculation, as demonstrated by an exaggerated effect of L-NMMA on the increase in arteriolar resistance, particularly that of the afferent (RA) arteriole, with higher basal nitric oxide (NO) activity (RA: high +1542 +/- 1065 versus medium +1024 +/- 718 versus low +675 +/- 861 dyne/s per cm; P < 0.001).


CONCLUSIONS
Our data clearly support experimental evidence linking NOS activity with increased glomerular filtration, and suggest that basal NO activity is also a major determinant of glomerular haemodynamics in the human renal vasculature.
Schlaich
Markus P
MP
Neurovascular Hypertension and Kidney Disease Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. markus.schlaich@baker.edu.au
Schmitt
Dominik
D
Ott
Christian
C
Schmidt
Bernhard Mw
BM
Schmieder
Roland E
RE
D000328:Adult; D015331:Cohort Studies; D004789:Enzyme Activation / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D012016:Reference Values; D015203:Reproducibility of Results; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase