Connexin 40 mediates the tubuloglomerular feedback contribution to renal blood flow autoregulation.
Connexins are important in vascular development and function. Connexin 40 (Cx40), which plays a predominant role in the formation of gap junctions in the vasculature, participates in the autoregulation of renal blood flow (RBF), but the underlying mechanisms are unknown. Here, Cx40-deficient mice (Cx40-ko) had impaired steady-state autoregulation to a sudden step increase in renal perfusion pressure. Analysis of the mechanisms underlying this derangement suggested that a marked reduction in tubuloglomerular feedback (TGF) in Cx40-ko mice was responsible. In transgenic mice with Cx40 replaced by Cx45, steady-state autoregulation and TGF were weaker than those in wild-type mice but stronger than those in Cx40-ko mice. N omega-Nitro-L-arginine-methyl-ester (L-NAME) augmented the myogenic response similarly in all genotypes, leaving autoregulation impaired in transgenic animals. The responses of renovascular resistance and arterial pressure to norepinephrine and acetylcholine were similar in all groups before or after L-NAME inhibition. Systemic and renal vasoconstrictor responses to L-NAME were also similar in all genotypes. We conclude that Cx40 contributes to RBF autoregulation by transducing TGF-mediated signals to the afferent arteriole, a function that is independent of nitric oxide (NO). However, Cx40 is not required for the modulation of the renal myogenic response by NO, norepinephrine-induced renal vasoconstriction, and acetylcholine- or NO-induced vasodilation.
Just
Armin
A
Department of Cell & Molecular Physiology, Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. armin.just@physiologie.uni-freiburg.de
Kurtz
Lisa
L
de Wit
Cor
C
Wagner
Charlotte
C
Kurtz
Armin
A
Arendshorst
William J
WJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017630:Connexins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D015291:Transforming Growth Factors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein
D000109:Acetylcholine; D017630:Connexins; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009638:Norepinephrine; D015291:Transforming Growth Factors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000097003:Gap Junction alpha-5 Protein