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Effects of pre‐contraction with endothelin‐1 on α 2 ‐adrenoceptor‐and (endothelium‐dependent) neuropeptide Y‐mediated contractions in the isolated vascular bed of the rat tail
Author(s) -
MacLean Margaret R.,
McGrath J. C.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12114.x
Subject(s) - phenylephrine , vasoconstriction , neuropeptide y receptor , endocrinology , medicine , endothelin receptor , neuropeptide , endothelin 1 , endothelins , endothelium , angiotensin ii , contraction (grammar) , agonist , perfusion , vasoconstrictor agents , chemistry , receptor , blood pressure
1 The pressor effects to bolus doses of the α 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 α 1 ‐adrenoceptor agonist phenylephrine induced dose‐dependent vasoconstriction, endothelin‐1 being some 10 4 times more potent than phenylephrine [log dose (mol) of the ED 50 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 ED 50 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 n m ) [log dose (mol) of the ED 50 for neuropeptide Y: −10.2 ± 0.2 ( n = 6)]. 4 Pre‐constriction‐induced pressor responses to UK‐14,304 were inhibited by 1 μ m 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 4 pmol or 8 pmol 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 ED 50 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 α 2 ‐adrenoceptor‐ and neuropeptide Y receptor‐activation are uncovered by agonist‐induced preconstriction including that to endothelin‐1. Neuropeptide Y‐induced vasoconstriction was endothelium‐dependent.