9652335

pubmed:Citation

2-3

This study concerned the effects and mechanisms of action of endothelin-1 on the cerebral circulation. Cerebral blood flow was electromagnetically measured in awake goats. Endothelin-1 (0.01-0.3 nmol) produced dose-dependent decreases in this flow (maximal reduction = 34%) and increases in cerebrovascular resistance (maximal increase = 74%) (P < 0.01). IRL 1620 (Suc-[Glu9, Ala11,15]endothelin-1-(8-21), agonist for endothelin ET(B) receptors, 0.01-0.3 nmol) slightly decreased cerebral blood flow. The effects of endothelin-1, but not those of IRL 1620, on cerebral blood flow were diminished by 50% during infusion of the antagonist for endothelin ET(A) receptors, BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-Trp), 2 nmol min(-1)), but not affected during infusion of the antagonist for endothelin ET(B) receptors, BQ-788 (N-[N-[N-[(2,6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-Leucyl-1-(met hoxycarbonyl)-D-tryptophyl]-Dnorleucine monosodium), 2 nmol min(-1)). Intravenous administration of NW-nitro-L-arginine methyl ester (L-NAME, 47 mg kg(-1)) or NW-nitro-L-arginine (L-NNA, 47 mg kg(-1)) reduced basal cerebral blood flow by 39 and 33%, increased cerebrovascular resistance by 108 and 98% and mean arterial pressure by 23 and 17%, and decreased heart rate by 27 and 25%, respectively (all at least P < 0.05). The increases in cerebrovascular resistance (as absolute values) induced by endothelin-1 were not affected during either L-NAME or L-NNA (as absolute values and percentages). Intravenous administration of meclofenamate (5 mg kg(-1)) did not change the cerebrovascular effects of endothelin-1 and IRL 1620. In isolated goat cerebral arteries under control, resting conditions, endothelin-1 (10(-11)-10(-7) M) induced concentration-dependent contractions (EC50 = 4.78 X 10(-9) M; maximal contraction = 3177+/-129 mg), whereas IRL 1620 (10(-11)-10(-7) M) produced no effect. This contraction produced by endothelin-1 was competitively blocked by BQ-123 (10(-7)-3 X 10(-6) M), and was not affected by BQ-788 (10(-6) and 10(-5) M). L-NAME (10(-4) M), meclofenamate (10(-5) M), indomethacin (10(-5) M), L-NAME (10(-4) M) plus meclofenamate (10(-5) M) and phosphoramidon (10(-4) M) did not affect the contraction in response to endothelin-1. Endothelium removal increased the response to endothelin-1, as well as the BQ-123 antagonism against endothelin-1 (pA2 values, 7.62 vs. 6.88; P < 0.01). In both intact and de-endothelized arteries precontracted with prostaglandin F2alpha endothelin-1 induced a further contraction, and IRL 1620 caused no effect. These results suggest that: (1) endothelin-1 produces cerebral vasoconstriction by activating endothelin ET(A) receptors probably located in smooth muscle; (2) endothelin ET(B) receptors, nitric oxide and prostanoids might be not involved in the cerebrovascular action of endothelin-1, and (3) endothelium removal may increase cerebrovascular reactivity by increasing sensitivity of endothelin ET(A) receptors to endothelin-1.

http://linkedlifedata.com/resource/pubmed/journal/1254354

http://linkedlifedata.com/resource/pubmed/chemical/BQ 788, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1, http://linkedlifedata.com/resource/pubmed/chemical/Endothelins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/IRL 1620, http://linkedlifedata.com/resource/pubmed/chemical/Meclofenamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester, http://linkedlifedata.com/resource/pubmed/chemical/Nitroarginine, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Piperidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin, http://linkedlifedata.com/resource/pubmed/chemical/cyclo(Trp-Asp-Pro-Val-Leu)

May

pubmed-author:DiéguezGG, pubmed-author:FernándezNN, pubmed-author:GómezBB, pubmed-author:García-VillalónA LAL, pubmed-author:GarcíaJ LJL, pubmed-author:MongeLL

8

NLM

199-211

pubmed-meshheading:9652335-Animals, pubmed-meshheading:9652335-Blood Pressure, pubmed-meshheading:9652335-Cerebrovascular Circulation, pubmed-meshheading:9652335-Cyclooxygenase Inhibitors, pubmed-meshheading:9652335-Endothelin-1, pubmed-meshheading:9652335-Endothelins, pubmed-meshheading:9652335-Enzyme Inhibitors, pubmed-meshheading:9652335-Goats, pubmed-meshheading:9652335-Heart Rate, pubmed-meshheading:9652335-Injections, Intravenous, pubmed-meshheading:9652335-Meclofenamic Acid, pubmed-meshheading:9652335-NG-Nitroarginine Methyl Ester, pubmed-meshheading:9652335-Nitroarginine, pubmed-meshheading:9652335-Oligopeptides, pubmed-meshheading:9652335-Peptide Fragments, pubmed-meshheading:9652335-Peptides, Cyclic, pubmed-meshheading:9652335-Piperidines, pubmed-meshheading:9652335-Receptors, Endothelin, pubmed-meshheading:9652335-Vascular Resistance

In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed.

Journal Article, In Vitro, Research Support, Non-U.S. Gov't