eNOS determines modulation of RBF autoregulation

Dautzenberg M, Keilhoff G, Just A.
Modulation of the Myogenic Response in Renal Blood Flow Autoregulation by NO Depends on eNOS, but not nNOS or iNOS.
J Physiol (London) 589.19: 4731–4744, 2011

Overview

This publication shows that the known modulation of RBF autoregulation by nitric oxide (NO) is determined by NO produced by eNOS, but not nNOS or iNOS. These findings suggest that it is mainly endothelial cells rather than macula densa, mesangial, or smooth muscle cells that are responsible for this effect of NO.

Links to the Journal and to PubMed

http://jp.physoc.org/content/589/19/4731.abstract

Nontechnical Summary as published in the Journal

Blood flow in the kidney is tightly regulated. This so-called autoregulation is essential for the function of the kidney as well as for its protection against damage and failure from high blood pressure. Autoregulation is caused by three mechanisms. The signaling molecule nitric oxide (NO) modulates the balance of these mechanisms, blunting the contribution of the fastest mechanism and increasing that of the others. Unknown is, where in the kidney the responsible NO is originating. Our data indicate that the cells of the inner lining of the blood vessels are by far the most important source of NO for this effect compared to other NO-producing cells in the relevant region of the kidney, such as macula densa, smooth muscle, or mesangial cells. The findings are important for understanding blood flow autoregulation in the kidney as well as kidney function and failure. 

Abstract as published in the Journal

Nitric oxide (NO) blunts the myogenic response (MR) in renal blood flow (RBF) autoregulation. We sought to clarify the roles of NO-synthase (NOS) isoforms, i.e. nNOS from macula densa, eNOS from the endothelium, and iNOS from smooth muscle or mesangium. RBF autoregulation was studied in rats and knockout (ko) mice in response to a rapid rise in renal artery pressure (RAP). The autoregulatory rise in renal vascular resistance within the first 6 s was interpreted as MR, from ~6 to ~30 s as tubuloglomerular feedback (TGF), and ~30 to ~100 s as third regulatory mechanism. In rats, nNOS inhibitor SMTC did not significantly affect MR (67±4 vs. 57±4 units). Inhibition of all NOS-isoforms by L-NAME in the same animals markedly augmented MR to 78±4 units. The same was found when SMTC was combined with Angiotensin II to reproduce the hypertension and vasoconstriction seen with L-NAME (58±3 vs. 54±7, L-NAME 81±2 units), or when SMTC was replaced by the nNOS-inhibitor NPA (57±5 vs. 56±7, L-NAME 79±4 units) or by the iNOS-inhibitor 1400W (50±1 vs. 55±4, LNAME 81±3 units). nNOS-ko mice showed the same autoregulation as wild-types (MR 36±4 vs. 38±3 units) and the same response to L-NAME (111±9 vs. 114±10 units). eNOS-ko had similar autoregulation as wild-types (44±8 vs. 33±4 units), but failed to respond to L-NAME (37±7 vs. 78±16 units). We conclude that the attenuating effect of NO on MR depends on eNOS, but not on nNOS or iNOS. In eNOS-ko mice MR is depressed by NO-independent means.