Background: 

Nitric oxide (NO) blunts the myogenic response (MR) in renal blood flow (RBF) autoregulation. We aimed to clarify the role of neuronal NO-synthase (nNOS) of macula densa cells and endothelial NOS (eNOS) of the afferent arteriole in eNOS- and nNOS-knockout (ko) mice.

Methods: 

Autoregulatory mechanisms were assessed from the response of renal vascular resistance to small rapid changes of renal artery pressure (AP). The response within the first 6 s was interpreted as MR, from 6 to 25 s as tubuloglomerular feedback (TGF), and 25 to 100 s as third regulatory mechanism.

Results: 

In wild-type (wt) mice the three mechanisms contributed 36±3, 49±6, and 27±4 units to autoregulation. LNAME elevated AP +25±4 mmHg and reduced RBF -47±4%; MR was augmented and TGF and third mechanism blunted to 92±11, 14±3, and 2±4 units. nNOS-ko showed similar AP (85±2 vs. all wt 91±1 mmHg), RBF (11±1 vs. 12±1 ml/min/g), and autoregulation (38±4, 60±6, 34±5 units) as wt. LNAME induced similar changes of AP (+32±6 mmHg), RBF (-56±3%), and autoregulation (115±11, 21±6, -3±7 units). eNOS-ko were hypertensive (AP=110±4 mmHg), while RBF (12±1 ml/min/g) and autoregulation (35±5, 57±5, 26±11 units) resembled wt. However, LNAME failed to elevate AP (+1±1 mmHg), reduce RBF (+16±8%) or augment MR (autoregulation: 29±5, 47±12, 30±3 units).

Conclusions: 

NO-dependent modulation of MR in RBF autoregulation depends on eNOS, but not nNOS. In eNOS-ko mice MR is blunted by NO-independent means.