Increased α1- and α2- adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischaemia

Y.P. Jarajapu, Paul Coats, John C. McGrath, A. MacDonald, Chris Hillier

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Recently, we have shown augmented contractile responses of skeletal muscle resistance arteries to noradrenaline in patients with critical limb ischemia. We investigated whether this increased sensitivity in skeletal muscle resistance arteries is due to either α1- or α2-adrenoceptor-mediated responses or both. Methods: Skeletal muscle resistance arteries were isolated from the proximal (non-ischemic) and distal (ischemic) parts of limbs amputated for critical limb ischemia and mounted on a small vessel wire myograph. Cumulative concentration response curves of the vessel segments to noradrenaline, phenylephrine and brimonidine were obtained in the presence or the absence of the selective antagonists, prazosin and RS79948. Results: Noradrenaline and phenylephrine produced almost equal maximal contractile responses. Brimonidine responses were smaller and were almost abolished by 0.1 μM RS 79948 while those of phenylephrine and noradrenaline were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephrine rightwards giving pKB values of 9.86 and 9.33, respectively. Maximum responses produced by all three agonists in distal vessels were significantly higher than those obtained in proximal vessels. Conclusions: Noradrenaline contractile responses in skeletal muscle resistance arteries are predominantly mediated by α1-adrenoceptors. Both α1- and α2-adrenoceptor-mediated responses are increased in the arteries from ischemic regions that may aggravate the decreased blood flow to the limbs due to arterial occlusion.
LanguageEnglish
Pages218-225
Number of pages8
JournalCardiovascular Research
Volume49
Issue number1
DOIs
Publication statusPublished - 1 Jan 2001

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Adrenergic Receptors
Norepinephrine
Skeletal Muscle
Ischemia
Extremities
Arteries
Phenylephrine
Prazosin
Brimonidine Tartrate
RS 79948-197

Keywords

  • adrenergic (ant)agonists
  • arteries
  • ischemia
  • receptors
  • vasoconstriction
  • dilation

Cite this

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title = "Increased α1- and α2- adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischaemia",
abstract = "Objective: Recently, we have shown augmented contractile responses of skeletal muscle resistance arteries to noradrenaline in patients with critical limb ischemia. We investigated whether this increased sensitivity in skeletal muscle resistance arteries is due to either α1- or α2-adrenoceptor-mediated responses or both. Methods: Skeletal muscle resistance arteries were isolated from the proximal (non-ischemic) and distal (ischemic) parts of limbs amputated for critical limb ischemia and mounted on a small vessel wire myograph. Cumulative concentration response curves of the vessel segments to noradrenaline, phenylephrine and brimonidine were obtained in the presence or the absence of the selective antagonists, prazosin and RS79948. Results: Noradrenaline and phenylephrine produced almost equal maximal contractile responses. Brimonidine responses were smaller and were almost abolished by 0.1 μM RS 79948 while those of phenylephrine and noradrenaline were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephrine rightwards giving pKB values of 9.86 and 9.33, respectively. Maximum responses produced by all three agonists in distal vessels were significantly higher than those obtained in proximal vessels. Conclusions: Noradrenaline contractile responses in skeletal muscle resistance arteries are predominantly mediated by α1-adrenoceptors. Both α1- and α2-adrenoceptor-mediated responses are increased in the arteries from ischemic regions that may aggravate the decreased blood flow to the limbs due to arterial occlusion.",
keywords = "adrenergic (ant)agonists, arteries, ischemia, receptors , vasoconstriction, dilation",
author = "Y.P. Jarajapu and Paul Coats and McGrath, {John C.} and A. MacDonald and Chris Hillier",
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Increased α1- and α2- adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischaemia. / Jarajapu, Y.P.; Coats, Paul; McGrath, John C.; MacDonald, A.; Hillier, Chris.

In: Cardiovascular Research, Vol. 49, No. 1, 01.01.2001, p. 218-225.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased α1- and α2- adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischaemia

AU - Jarajapu, Y.P.

AU - Coats, Paul

AU - McGrath, John C.

AU - MacDonald, A.

AU - Hillier, Chris

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Objective: Recently, we have shown augmented contractile responses of skeletal muscle resistance arteries to noradrenaline in patients with critical limb ischemia. We investigated whether this increased sensitivity in skeletal muscle resistance arteries is due to either α1- or α2-adrenoceptor-mediated responses or both. Methods: Skeletal muscle resistance arteries were isolated from the proximal (non-ischemic) and distal (ischemic) parts of limbs amputated for critical limb ischemia and mounted on a small vessel wire myograph. Cumulative concentration response curves of the vessel segments to noradrenaline, phenylephrine and brimonidine were obtained in the presence or the absence of the selective antagonists, prazosin and RS79948. Results: Noradrenaline and phenylephrine produced almost equal maximal contractile responses. Brimonidine responses were smaller and were almost abolished by 0.1 μM RS 79948 while those of phenylephrine and noradrenaline were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephrine rightwards giving pKB values of 9.86 and 9.33, respectively. Maximum responses produced by all three agonists in distal vessels were significantly higher than those obtained in proximal vessels. Conclusions: Noradrenaline contractile responses in skeletal muscle resistance arteries are predominantly mediated by α1-adrenoceptors. Both α1- and α2-adrenoceptor-mediated responses are increased in the arteries from ischemic regions that may aggravate the decreased blood flow to the limbs due to arterial occlusion.

AB - Objective: Recently, we have shown augmented contractile responses of skeletal muscle resistance arteries to noradrenaline in patients with critical limb ischemia. We investigated whether this increased sensitivity in skeletal muscle resistance arteries is due to either α1- or α2-adrenoceptor-mediated responses or both. Methods: Skeletal muscle resistance arteries were isolated from the proximal (non-ischemic) and distal (ischemic) parts of limbs amputated for critical limb ischemia and mounted on a small vessel wire myograph. Cumulative concentration response curves of the vessel segments to noradrenaline, phenylephrine and brimonidine were obtained in the presence or the absence of the selective antagonists, prazosin and RS79948. Results: Noradrenaline and phenylephrine produced almost equal maximal contractile responses. Brimonidine responses were smaller and were almost abolished by 0.1 μM RS 79948 while those of phenylephrine and noradrenaline were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephrine rightwards giving pKB values of 9.86 and 9.33, respectively. Maximum responses produced by all three agonists in distal vessels were significantly higher than those obtained in proximal vessels. Conclusions: Noradrenaline contractile responses in skeletal muscle resistance arteries are predominantly mediated by α1-adrenoceptors. Both α1- and α2-adrenoceptor-mediated responses are increased in the arteries from ischemic regions that may aggravate the decreased blood flow to the limbs due to arterial occlusion.

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