Pharmacological characterization of postjunctional α‐adrenoceptors in cerebral arteries from the sheep

Gaw, Allan; Wadsworth, R. M.

doi:10.1111/j.1476-5381.1989.tb14601.x

Cited by 14 publications

(8 citation statements)

References 16 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…0 serotonin (35). In the present study, neither propranolol nor LNAME completely restored the reactivity of newborn lamb MCA to NE to that observed for preterm fetuses.…”

Section: Discussioncontrasting

confidence: 81%

Nitric Oxide and β-Adrenergic Mechanisms Modify Contractile Responses to Norepinephrine in Ovine Fetal and Newborn Cerebral Arteries

Lc¹,

Moliken²,

Russo³

1995

Pediatr Res

View full text Add to dashboard Cite

Ovine fetal cerebral artcries exhibit an enhanced contractile response to norepinephrine (NH) compared with newborns and adults. It is possible that P-adrenergic receptors and/or nitric oxide (NO), a putative endothelium-dependent relaxing factor, differentially modulate cerebrovascular responsiveness to NE as a function of developmcnt. 'l'he present study evaluated the effect of thc P-adrenoceptor antagonist, propranolol, and the NO synthasc inhibitor, N~-nitro-I.-arginine methyl estcr (I,NAME), on the contractile response of isolated middle cerebral artery (MCA) and basilar artery (BA) to NIi during fetal development. MCAs isolated from four preterm fetal lambs (105 d of gestation), seven near-term fetal lambs (125-130 d of gestation), and eight newborn lambs (2-7 d of age) were evaluated using organ baths. BAS isolated from the near-term fetal and newborn lambs were also evaluated. Contractile reactivity of MCAs to NB dccreased significantly during fetal maturation as manifested by a marked decrease in F,,,,, (maximal relative contractile force generated) and an increase in EC,,, (F,,, -100 -+ 7,41 -+ 7, and 28 r 8% of KC1 contraction; HC,,,-0.14 + 0.03, 1.09 :+-0.36, and 1.07 + 0.22 pM for preterm fetus, near-term fetus, and newborn lamb MCAs, respectively, p 5 0.05). Propranolol treatment M) increased F,,,, (2-fold) only for newborn lamb MCAs. Pretreatnlent with LNAME (10 '' M) markedly enhanced rhc contractile T h e activation of the sympatho-adrenal axis is considered to be unimportant to the regulation of cerebral blood flow in adults (1, 2); however, such is not necessarily the case for the fetus and neonate. Activation of sympathetic nerves constricted cerebral arterioles and decreased cerebral blood flow in newborn and Letal animal models (3-6). In addition, fetal cerebral arteries, both in vivo and in vitro, exhibited cnhanced reactivity to the sympathetic neurotransmitter, norepinephrine (NE) (7-9). 'l'hese reports suggest that the neuroeffector system may be an important factor with respect to the developing cerebral response to NE (7-fold decrease in EC,, and 2-fold increase in F',,,,, p < 0.05) for near-term fetus MCAs, whereas preterm fetus and newborn lamb MCAs were unaffected by the inhibitor. 13.4s were unresponsive to NE except for near-term fetus BAS in the presence of LNAMIX. 'l'he eEcct of NO-synthase inhibition on NE contractility was dependent on developmental age, being prominent near term. The data suggest that, in the more mature fetus, NO, presumably derived from endothelium, bchaves as a functional antagonist to sympathetic vasoconstriction of the cerebrovasculature, and its apparent absence permits unrepressed sympathetic vasoconstriction in the premature brain. (Pediatr Hes 38: 237-242, 1995) Abbreviations NE:, norepinephrine NO, nitric oxide MCA, middle cerebral artery BA, basilar artery LNAME, N~-nitro-L-arginine methyl ester EC,,, effective drug concentration inducing 50% of maximal response F,,,, maximal force generated in response to drug circulation and indicate t...

show abstract

“…0 serotonin (35). In the present study, neither propranolol nor LNAME completely restored the reactivity of newborn lamb MCA to NE to that observed for preterm fetuses.…”

Section: Discussioncontrasting

confidence: 81%

Nitric Oxide and β-Adrenergic Mechanisms Modify Contractile Responses to Norepinephrine in Ovine Fetal and Newborn Cerebral Arteries

Lc¹,

Moliken²,

Russo³

1995

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…A heterogeneous distribution of both adrenoceptor types may also be responsible for the regional selectivity of the NA-effect. A regional heterogeneity in the relative proportion of adrenoceptors mediating constriction or relaxation has been put forward in order to explain results of experiments on regional changes of cerebral blood flow (Edvinsson et al, 1979) and could explain the findings of regional selectivity in vessels of cats (Harder et al, 1981;Hamel et al, 1988) and sheep (Gaw & Wadsworth, 1989). Ayajiki & Toda (1990;1992) described NA-induced contractile effects in rostral and relaxant effects in caudal bovine cerebral arteries.…”

Section: Regional Variations Of Noradrenaline Effects In Cerebral Artmentioning

confidence: 99%

Endothelium‐dependent noradrenaline‐induced relaxation of rat isolated cerebral arteries: pharmacological characterization of receptor subtypes involved

Hempelmann

Ziegler

1993

British J Pharmacology

View full text Add to dashboard Cite

1 The endothelium-dependence of catecholamine-induced relaxation of rat cerebral arteries was investigated in vitro. 2 In the basilar artery (BA), the maximal relaxant response was most pronounced with noradrenaline (NA), less with isoprenaline (Iso), and only very little with terbutaline. Methoxamine and the a2-adrenoceptor selective agonists BHT 933 and clonidine, had no relaxant effect. 3 In BA, the relaxation by NA or Iso was markedly attenuated by N@-nitro-L-arginine (L-NOARG) 10-4 M. Short term perfusion of the vessels by Triton X 100 (1:1 000) suppressed the NA-induced relaxation. 4 The relaxation induced by NA or Iso was markedly reduced in presence of L-NOARG in the posterior, medial and anterior cerebral artery.5 In BA, NA-induced relaxation was non-competitively inhibited by propranolol, atenolol, and the Pland P2-adrenoceptor selective antagonists, CGP 20712 A and ICI 118551.6 The relaxant NA-effect was not affected by prazosin but was non-competitively blocked by phentolamine. 7 The Iso-induced relaxation was competitively blocked by propranolol, whereas atenolol, CGP 20712 A and ICI 118551 caused a non-competitive inhibition. 8 The experiments indicate that the catecholamine-induced relaxation in rat isolated cerebral arteries depends upon the endothelium. They suggest that the NA-induced relaxation of BA is mediated by different a-and ,-adrenoceptors and that the Iso-induced relaxation is mediated by different P-receptors.The findings would also be compatible with the idea of a receptor type which cannot be characterized by the pharmacological tools that we have used.

show abstract

“…Since 5‐HT‐induced constriction of ovine cerebral arteries is mediated in part by 5‐HT 2 and 5‐HT 1 receptors ( Gaw et al. 1990) it is possible that activation of these receptors following IT injections of agonists could reduce blood flow in the spinal region.…”

Section: Discussionmentioning

confidence: 99%

“…There was also a 5‐HT 1 mediated constriction of these vessels, induced by sumatriptan. However, 5‐HT 3 receptors were not involved ( Gaw et al. 1990).…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive effects of intrathecal 5-HT agonists in sheep

Roberts

Livingston

Waterman-Pearson

2000

Veterinary Anaesthesia and Analgesia

View full text Add to dashboard Cite

Pharmacological characterization of postjunctional α‐adrenoceptors in cerebral arteries from the sheep

Cited by 14 publications

References 16 publications

Nitric Oxide and β-Adrenergic Mechanisms Modify Contractile Responses to Norepinephrine in Ovine Fetal and Newborn Cerebral Arteries

Nitric Oxide and β-Adrenergic Mechanisms Modify Contractile Responses to Norepinephrine in Ovine Fetal and Newborn Cerebral Arteries

Endothelium‐dependent noradrenaline‐induced relaxation of rat isolated cerebral arteries: pharmacological characterization of receptor subtypes involved

Antinociceptive effects of intrathecal 5-HT agonists in sheep

Contact Info

Product

Resources

About