The effect of L-NAME on intra- and inter-nephron synchronization

• Published in: European journal of pharmaceutical sciences 2009-01, Vol.36 (1), p.39-50
• Main Authors: Sosnovtseva, O.V., Pavlov, A.N., Pavlova, O.N., Mosekilde, E., Holstein-Rathlou, N.-H.
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Arterioles - drug effects; Arterioles - physiology; Enzyme Inhibitors - pharmacology; Homeostasis - drug effects; Hypertension, Renal - drug therapy; Hypertension, Renal - physiopathology; Kidney Glomerulus - drug effects; Kidney Glomerulus - physiology; Kidney Tubules - drug effects; Kidney Tubules - physiology; Kinetics; L-NAME; Male; Nephron synchronization; Nephrons - blood supply; Nephrons - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Renal Artery - drug effects; Renal Circulation - drug effects; TGF mechanism
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2008.10.019

Kidney autoregulation involves complicated intra- and inter-nephron synchronization phenomena among oscillatory modes produced, respectively, by the tubuloglomerular feedback (TGF) mechanism and by the myogenic regulation of the afferent arteriolar blood flow. The present study aims at examining to what extent these phenomena are reflected in the overall blood flow to the kidney and how they are affected by intravenous administration of nitro- l-arginine-methyl-ester (L-NAME), a potent NO synthesis inhibitor. Wavelet analysis is applied to detect rhythmic activity at the level of the renal artery and compare the observed fluctuations with blood flow variations recorded from efferent arterioles of individual nephrons. We show that administration of L-NAME increases the gain in both the TGF and the myogenic oscillations, and that both normotensive and hypertensive rats demonstrate reduced stability of the various rhythms. This implies that L-NAME, besides strengthening the gain in the individual feedback mechanisms, also causes more frequent transitions among the various synchronization states. In a broader perspective the purpose of the study is to demonstrate the significance of complex dynamic phenomena in the normal regulation of physiological systems as well as in their response to drugs.