Effect of endothelium removal on the vasoconstrictor response to neuronally released 5-hydroxytryptamine and noradrenaline in the rat isolated mesenteric and femoral arteries.
1. The role of the vascular endothelium in the vasoconstrictor response to transmural nerve stimulation (TNS) was studied in isolated ring segments of rat mesenteric and femoral arteries. 2. In both types of artery, TNS (1 to 16 Hz) produced frequency-dependent vasoconstriction, which was abolished by 100 nM tetrodotoxin, 10 microM guanethidine or 10 nM prazosin, indicating that the response was mediated by endogenous noradrenaline (NA) released from noradrenergic nerves. NA-mediated vasoconstriction in response to TNS was significantly potentiated by removal of the endothelium. 3. In the presence of 10 nM prazosin, the reduced vasoconstriction in response to TNS was restored by incubation with 10 microM 5-hydroxytryptamine (5-HT) for 20 min. Restoration of the response to TNS was markedly attenuated by treatment with 10 nM ketanserin, 100 nM tetrodotoxin, or 10 microM guanethidine, indicating that the restored response was mediated by 5-HT released from noradrenergic nerves. Vasoconstriction mediated by 5-HT in response to TNS was not modified by removal of the endothelium. 4. In both types of artery with intact endothelium, treatment with 3 microM methylene blue potentiated the NA-mediated contractile response to TNS, but did not potentiate the 5-HT-mediated response to TNS. 5. In both types of artery, the contractile responses to exogenous NA and 5-HT were potentiated by removal of the endothelium. 6. These results suggest that endothelial cells regulate neurogenic vasoconstriction by releasing endothelium-derived relaxing factor. Furthermore, it appears likely that the response to neuronally released 5-HT is not affected by the endothelium.
Urabe
M
M
Department of Pharmacology, Miyazaki Medical College, Japan.
Kawasaki
H
H
Takasaki
K
K
D000818:Animals; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D012701:Serotonin; D011189:Potassium Chloride; D008751:Methylene Blue; D009638:Norepinephrine