title: Modulation of the myogenic response in renal blood flow autoregulation by NO depends on endothelial nitric oxide synthase (eNOS), but not neuronal or inducible NOS.
abstract: 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. neuronal NOS (nNOS) from macula densa, endothelial NOS (eNOS) from the endothelium, and inducible NOS (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 the third regulatory mechanism. In rats, the 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 units, l-NAME 81 ± 2 units), or when SMTC was replaced by the nNOS inhibitor NPA (57 ± 5 vs. 56 ± 7 units, l-NAME 79 ± 4 units) or by the iNOS inhibitor 1400W (50 ± 1 vs. 55 ± 4 units, l-NAME 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.
authors.affiliation: Physiologisches Institut, Abt. 1, Albert-Ludwigs-Universität Freiburg, Engesser Strasse 4, Freiburg im Breisgau, Germany. marcel.dautzenberg@frias.uni-freiburg.de
authors.forename: Marcel
authors.initials: M
authors.lastname: Dautzenberg
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Armin
authors.initials: A
authors.lastname: Just
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester