title: Effects of pre-contraction with endothelin-1 on alpha 2-adrenoceptor- and (endothelium-dependent) neuropeptide Y-mediated contractions in the isolated vascular bed of the rat tail.
abstract: 1. The pressor effects to bolus doses of the alpha 2-adrenoceptor agonist UK-14,304 were studied in the isolated vascular bed of the perfused rat tail before and after increasing the perfusion pressure with infusions of endothelin-1. Those of neuropeptide Y were studied before and after pre-constriction with endothelin-1 or 5-hydroxytryptamine. The pressor effects of neuropeptide Y were studied before and after functional disruption of the endothelium with the detergent CHAPS. 2. Endothelin-1 and the alpha 1-adrenoceptor agonist phenylephrine induced dose-dependent vasoconstriction, endothelin-1 being some 10(4) times more potent than phenylephrine [log dose (mol) of the ED50 for endothelin-1 and phenylephrine: -11.8 +/- 0.2 (n = 7), -8.2 +/- 0.2 (n = 5) respectively]. 3. Under control conditions, at basal perfusion pressures, UK-14,304 and neuropeptide Y were virtually inactive as vasoconstrictors. Following a sustained increase in perfusion pressure by infusions of endothelin-1 (2.5-10 nM at 0.8 ml min-1), however, both UK-14,304 and neuropeptide Y induced dose-dependent pressor responses and both were some 10(2) times more potent than phenylephrine [log dose (mol) of the ED50 for UK-14304 and neuropeptide Y: -10 +/- 0.5 (n = 6), -10.3 +/- 0.4 (n = 6) respectively]. Responses to neuropeptide Y also were uncovered when vascular tone was increased with 5-hydroxytryptamine (5-20 nM) [log dose (mol) of the ED50 for neuropeptide Y: -10.2 +/- 0.2 (n = 6)]. 4. Pre-constriction-induced pressor responses to UK-14,304 were inhibited by 1 microM rauwolscine whilst those to neuropeptide Y were inhibited by disruption of the endothelium. Removal of the endothelium had no significant effect on the pressor responses to 4pmol or 8pmol endothelin-1 and had no effect on the increase in perfusion pressure induced by the endothelin-1 infusions but did decrease the time-course of pressor responses to bolus injections of endothelin-1. Endothelial disruption had no significant effect on the vasoconstriction induced by all but one of the doses of phenylephrine administered [log dose (mol) of the ED5o for phenylephrine after CHAPS: -8.6 + 0.2 (n = 5)], indicating that the responsiveness of the vascular smooth muscle was not destroyed by CHAPS. This treatment did, however, slow the onset and prolong the time course of the phenylephrine-induced responses. 5. These results indicate that, in the isolated vascular bed of the rat tail, pressor responses to both alpha 2-adrenoceptor- and neuropeptide Y receptor-activation are uncovered by agonist-induced preconstriction including that to endothelin-1. Neuropeptide Y-induced vasoconstriction was endotheliumdependent.
authors.affiliation: Autonomic Physiology Unit, Institute of Physiology, University of Glasgow.
authors.forename: M R
authors.initials: MR
authors.lastname: MacLean
authors.forename: J C
authors.initials: JC
authors.lastname: McGrath
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D002793:Cholic Acids / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009478:Neuropeptide Y / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D013623:Tail / Q000098:blood supply; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D002793:Cholic Acids; D016232:Endothelins; D009478:Neuropeptide Y; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate