Importance of nitric oxide in the control of renal hemodynamics

The kidney vasculature is under tonic control by nitric oxide (NO) and in cortex, NO controls R(A) and K-f. Systemic NO inhibition leads to systemic hypertension, increases in R(E), mediated by Ang II and ET, and direct effects on R(A) and K-f. The relationship between NO and other vasoconstrictor systems is variable. In the conscious relaxed animal, vasoconstrictor activity is low, yet acute NO inhibition leads to presser and renal vasoconstrictor reponses. At physiologic levels, ET unexpectedly is a renal vasodilator, possibly via NO generation at R(A). When vasoconstrictor activity is high, NO is very important in maintenance of renal perfusion. Chronic L-NAME produces dose dependent systemic and glomerular capillary hypertension and eventual proteinuria and glomerular damage. NO deficiency is key in this process, although the hypertension becomes refractory to L-arginine administration and dependent on Ang II and the SNS, by mechanisms not yet defined. In contrast, the renal vasculature remains fully responsive to L-arginine, suggesting that presser and renal vascular responses to chronic NO inhibition are separately regulated. NO generated from iNOS does not normally control BP or renal hemodynamics. The relative contributions of NO from bNOS and eNOS, and importance of NOS in different locations in the kidney, remain to be determined.