Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries.
Experiments were designed to determine whether chronic increases in arterial blood flow alter production of or response to nitric oxide and endothelin. Canine femoral arteries proximal to an arteriovenous fistula- and from the contralateral sham-operated blood vessels were removed, cut into rings, and suspended for measurement of isometric force in organ chambers. The remainder of the artery was homogenized for measurement of endothelin content by radioimmunoassay. NG-monomethyl-L-arginine (10(-4) M) caused concentration-dependent increases in tension only in fistula-operated arteries. Endothelium-dependent relaxations to acetylcholine and BHT-920 were greater in fistula- compared with sham-operated arteries. These differences were reduced by the arginine analogue. Pertussis toxin (100 ng/ml) inhibited relaxations to acetylcholine only in fistula-operated arteries and to BHT-920 only in sham-operated arteries. Contractions to endothelin-1 were greater in fistula- compared with sham-operated arteries. These results suggest that chronic increases in blood flow enhance the tonic and receptor-stimulated production of nitric oxide and its release by receptors coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins. Furthermore, chronic increases in blood flow may either inhibit the production of endothelin or promote its depletion from endothelial cells while simultaneously increasing the sensitivity of the smooth muscle to its contractile effects.
Miller
V M
VM
Department of Surgery and Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Burnett
J C
JC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D037342:Pertussis Toxin; D012039:Regional Blood Flow; D013268:Stimulation, Chemical; D013997:Time Factors; D014661:Vasoconstriction; D014664:Vasodilation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016232:Endothelins; D010566:Virulence Factors, Bordetella; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D037342:Pertussis Toxin