VASCULAR BIOLOGY - HEMODYNAMICS - HYPERTENSION Neuronal nitric oxide synthase inhibition sensitizes the tubuloglomerular feedback mechanism after volume expansion

Russell Brown; Anna Ollerstam; A. Erik G. Persson
April 2004
Kidney International;Apr2004, Vol. 65 Issue 4, p1349
Academic Journal
Neuronal nitric oxide synthase inhibition sensitizes the tubuloglomerular feedback mechanism after volume expansion. Background. In the kidney the neuronal isoform of nitric oxide synthase (nNOS) is located in the macula densa cells. These cells are known to be the sensor in the tubuloglomerular feedback. During volume expansion (VE), the tubuloglomerular feedback response is attenuated, allowing increased water and salt excretion. This study addressed the question whether inhibition of nNOS reestablishes the tubuloglomerular feedback response caused by acute extracellular VE. Methods. In rats, VE was achieved by infusion of isotonic saline solution at 50 mL/hour * kg body weight. When urine flow was stabilized, the tubuloglomerular feedback response was evaluated by measuring changes in proximal tubular stop-flow pressure (PSF) in response to various loop of Henle perfusion rates. The loop of Henle was perfused with artificial ultrafiltrate and with addition of 1 mol/L non-specific NOS inhibitor, Nω-nitro- l-arginine methyl ester (L-NAME). In additional rats the nNOS inhibitor, 7-nitro indazole (7-NI), was given intraperitoneally. Single nephron glomerular filtration rate (SNGFR) was also measured. GFR was determined after VE and nNOS inhibition. Results. Acute VE decreased ΔPSF and ΔSNGFR while increasing the turning point, indicating decreased sensitivity of tubuloglomerular feedback response. After administration of L-NAME or 7-NI, ΔPSF was maximally sensitized and the turning point and ΔSNGFR were restored. GFR decreased after VE and nNOS inhibition compared to that after VE alone. Conclusion. These results suggest that a functioning nitric oxide system, especially through the nNOS, is important in mediating normal renal responses and that increased production of and/or sensitivity to nitric oxide during sustained VE plays an important role in the adaptive mechanism of the tubuloglomerular feedback.


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