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NDT Advance Access published online on March 5, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh187
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received October 31, 2003
Accepted February 4, 2004

Original Article

The role of nitric oxide in the regulation of glomerular haemodynamics in humans

Christian Delles 1, Arnfried U. Klingbeil 1, Markus P. Schneider 1, Renate Handrock 2, Tim Schäufele 1, Roland E. Schmieder 1*

1 Department of Medicine IV/4, University of Erlangen-Nürnberg, Germany
2 Novartis Pharma GmbH, Nürnberg, Germany

* To whom correspondence should be addressed. E-mail: roland.schmieder{at}rzmail.uni-erlangen.de.



  Abstract

Background. According to experimental data, the afferent glomerular arteriole is particularly under control of nitric oxide (NO). By use of pharmacological manoeuvres, we examined whether this finding holds true in the human renal circulation in vivo.

Methods. Seventy-seven volunteers (aged 50±9 years) with mild to moderate essential hypertension (n = 57) or arterial normotension (n = 20) were examined. Basal NO activity in the renal circulation was assessed by the change of renal plasma flow (RPF) through systemic infusion of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). Hypertensive patients were treated over 8 weeks with either the calcium-channel blocker amlodipine or the AT1-receptor blocker valsartan, primarily dilating the afferent and efferent arteriole, respectively. Subsequently, renal haemodynamics and NO activity in the renal circulation were determined again.

Results. L-NMMA reduced RPF in normotensive (by 57±70 ml/min/1.73 m2; P<0.01) and hypertensive subjects (by 46±56 ml/min/1.73 m2; P<0.001) with no significant difference between the two groups. The decrease of RPF through L-NMMA was closely related with the glomerular filtration rate (GFR; r = 0.39, P<0.001). Administration of amlodipine increased GFR by 7.1±12.1 ml/min/1.73 m2; (P<0.01) and in parallel reduced the response of RPF to L-NMMA to 19±48 ml/min/1.73 m2; (P<0.05). In contrast, valsartan maintained GFR and left the response of RPF to L-NMMA unchanged.

Conclusions. NO plays an important role in the regulation of human glomerular haemodynamics, probably with a greater contribution to afferent than to efferent arteriolar tone in man.

Keywords: angiotensin-II receptor blocker, calcium-channel blocker, glomerular haemodynamics, humans, nitric oxide


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