Higher sensitivity of cerebral arteries isolated from premature and newborn baboons to adrenergic and cholinergic stimulation

Hayashi, Shigehiro; Park, Myung K.; Kuehl, Thomas J.

doi:10.1016/0024-3205(84)90108-5

Cited by 44 publications

(27 citation statements)

References 11 publications

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“…One possible explanation for the failure of others to detect significant a-adren ergic receptors on cerebral vessels of adult pigs is that a-adrenoceptors are more important in regulating cerebrovascular tone in neonatal animals than in adults. This view is consistent with a finding by Hayashi et al [11] who reported that cerebral arteries of fetal and newborn baboons con stricted more in response to exogenous norepinephrine than similar vessels from adult baboons. However, it has also been reported that in isolated cerebral arteries in rabbits, constrictor responses to norepinephrine are greater in adults than in neonates [22].…”

Section: Discussionsupporting

confidence: 82%

Postjunctional Alpha(2)-Adrenoceptors in Pial Arteries of Anesthetized Newborn Pigs

Busija

Leffler²

1987

Dev Pharmacol Ther

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The purpose of this study was to characterize the nature of the postjunctional α-adrenoceptors (α(1) versus α(2)) in the cerebral circulation of anesthetized newborn pigs. Diameters of piai arteries in anesthetized piglets, 1-6 days old, were examined using a 'closed' cranial window. We examined sympathetically mediated constriction of pial arteries in the presence and absence of α(1) (prazosin) or α(2)- (yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Initial experiments demonstrated that prazosin and yohimbine attenuated constriction of piai arteries during topical administration to the piai surface of phenylephrine and clonidine, respectively. In one group, electrical stimulation of the ipsilateral superior cervical ganglion reduced piai arterial diameter from 176 ± 26 (mean ± SEM) to 153 ± 24 μm, and this response was unaffected by prior administration of prazosin. In a second group, sympathetic nerve stimulation reduced piai arterial diameter from 175 ± 23 to 148 ± 19 μm, and this response was abolished by prior administration of yohimbine. After administration of yohimbine, piai arteries still constricted in response to topical phenylephrine and arterial hypertension. We conclude that sympathetic nerve stimulation in anesthetized newborn pigs constricts pial arteries via (α(2)-adrenoceptors.

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Section: Discussionsupporting

confidence: 82%

Postjunctional Alpha(2)-Adrenoceptors in Pial Arteries of Anesthetized Newborn Pigs

Busija

Leffler²

1987

Dev Pharmacol Ther

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“…These features include a reduced capacity to elicit maximal contraction, limited receptor reserve, reduced NE sensitivity, possible expression of unique a-adrenoceptor subtypes, relatively small vasoconstrictor responses to sympathetic stimulation, and when sympathetic vasoconstriction is present, it is limited to large arteries. The present study along with previous reports (4,6,30,31), however, demonstrate a remarkable capacity for sympathetic regulation of cerebral blood flow during the perinatal period that is specifically diminished as the animals mature (7)(8)(9)28). Indeed, preterm fetal lamb MCA exhibited a NE sensitivity (EC,, = 1.4 X 10F7 M) and a capacity to elicit a maximal contraction (100% of KC1 contraction) that were virtually identical to that normally attributed to noncerebral arteries (1).…”

Section: Discussionmentioning

confidence: 64%

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

Lc¹,

Moliken²,

Russo³

1995

Pediatr Res

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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...

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“…In the cerebral circulation, this immaturity may be particularly important, because it may contribute to the high incidence of cerebrovascular complications observed in neonates (2,3). Among the few studies that have directly examined maturational changes in cerebral arteries, however, most have found that vasoconstrictor reactivity is generally higher in immature than in mature cerebral arteries (1,(4)(5)(6). Thus, the high incidence of neonatal cerebrovascular complications seems not to be a consequence of a deficit in the ability of cerebral arteries to respond to vasoconstrictor stimuli.…”

mentioning

confidence: 99%

Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries

et al. 1994

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The present experiments examine the effects of maturation on cyclic GMP (cGMP)-mediated vasodilation in 688 segments of common carotid (COM) and basilar (BAS) arteries taken from newborn (3-to 7-d-old) and nonpregnant adult sheep. The main finding is that maximum efficacy for relaxation decreased with maturation in both artery types for the nitric oxide releasing vasodilators S-nitroso-N-acetyl-penicillamine and nitroglycerin. These decreases could not be explained by changes in the -log ED,, concentrations for either vasodilator. Determination of the time course of cGMP responses to S-nitroso-Nacetyl-penicillamine or nitroglycerin at 10 FM revealed that the peak cGMP responses to these agents (range: 5.3 2 0.8 to 8.3 a 1.6 pmollmg of protein) also did not vary significantly with age. However, cGMP attained peak values more rapidly in adult (COM: 50 s; BAS 30 s) than in newborn (COM: 60-80 s: BAS, 4 M 0 s) segments and returned to baseline more slowly in newborn than in adult segments, suggesting that maturation accelerates cGMP turnover. Correspondingly, baseline levels of cGMP were In most arteries, vascular structure and function are immature at birth and change markedly during early postnatal life (1). In the cerebral circulation, this immaturity may be particularly important, because it may contribute to the high incidence of cerebrovascular complications observed in neonates (2, 3). Among the few studies that have directly examined maturational changes in cerebral arteries, however, most have found that vasoconstrictor reactivity is generally higher in immature than in mature cerebral arteries (1, 4-6). Thus, the high incidence of neonatal cerebrovascular complications seems not to be a consequence of a deficit in the ability of cerebral arteries to respond to vasoconstrictor stimuli. Alternatively, it remains possible that altered mechanisms of cerebral vasorelaxation may be involved. If Supported by PHs Grant HL11347 and Grant 92-293A from the American Heart Association.higher in newborn (COM: 1.0 -' 0.1; BAS: 3.3 0.5 pmol/mg of protein) than in adult (COM: 0.3 2 0.1; BAS: 1.7 ? 0.2 pmollmg of protein) segments. Despite these differences in cGMP time course, rates of relaxation in response to S-nitroso-N-acetyl-penicillamine and nitroglycerin did not vary significantly with age, indicating that the temporal relation between cGMP and relaxation is different in newborn and adult arteries. Together, these results suggest that the capacity of the cGMP pathway to produce relaxation is attenuated by maturation through changes possibly related to cGMP turnover. Abbreviations ANOVA, analysis of variance cGMP, cyclic GMP pD,, the negative logarithm of the concentration of an agent that produces half its maximal effect SNAP, S-nitroso-N-acetyl-penicillamine NG, nitroglycerin newborn arteries have a greater propensity to relax, they may be less capable of resisting the vascular injury and rupture often associated with insults, such as asphyxia and transient hypertension, that markedly elevate cerebral perfusion. Me...

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Higher sensitivity of cerebral arteries isolated from premature and newborn baboons to adrenergic and cholinergic stimulation

Cited by 44 publications

References 11 publications

Postjunctional Alpha(2)-Adrenoceptors in Pial Arteries of Anesthetized Newborn Pigs

Postjunctional Alpha(2)-Adrenoceptors in Pial Arteries of Anesthetized Newborn Pigs

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

Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries

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