Effects of Naloxone on Canine Cerebral Vascular Smooth Muscle

Sasaki, Tomio; Kassell, Neal F.; Turner, Donn M.; Maixner, William; Torner, James C.; Coester, Hans C.

doi:10.1038/jcbfm.1984.24

Cited by 21 publications

(9 citation statements)

References 18 publications

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“…Recently, it has been reported that the opioid antagonist naloxone selectively inhibited the constrictor response of canine basilar artery to norepinephrine while it failed to alter the response to phenylephrine or clonidine. 22 These results also confirm the atypical nature of receptors which mediate the constrictor response of canine basilar artery to norepinephrine.…”

Section: Discussionsupporting

confidence: 76%

Pharmacological comparison of isolated monkey and dog cerebral arteries.

Sasaki

Kassell

Torner

et al. 1985

Stroke

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SUMMARY Pharmacological differences between canine and monkey basilar arteries were studied in vitro. The constrictor response of canine basilar artery to either norepinephrine or an a ( -adrenoceptor agonist phenylephrine was partly inhibited by an a 2 -adrenoceptor antagonist yohimbine but not by an a,-adrenoceptor antagonist prazosin. The contraction elicited by an » 2 -adrenoceptor agonist clonidine was inhibited by neither prazosin nor yohimbine. These results suggest that the receptors in canine basilar artery which mediate norepinephrine-induced contraction are different from classical a, or a 2 -adrenoceptors, although they more closely resemble the a 2 -rather than the a|-subtype. Using monkey basilar artery, phenylephrine produced the same amplitude of maximum contractile response as norepinephrine, though a much higher concentration of phenylephrine than norepinephrine was needed in order to elicit that maximum response. Clonidine did not elicit contractions. The contraction induced by norepinephrine was markedly suppressed by both prazosin and yohimbine in a noncompetitive fashion. The constrictor response of monkey basilar artery to norepinephrine, therefore, appears to be mediated by «,-like adrenoceptors. Comparison of ED50 values for thromboxane A2 revealed that the monkey basilar artery was more sensitive to thromboxane A2 than that of the canine. Prostaglandin F2a produced a larger maximum contraction in monkey basilar arteries than in canine basilar arteries, although the ED 50 values for monkey basilar arteries were larger than those for canine basilar arteries. The ED 50 values for serotonin in canine basilar arteries were a little less than those for monkey basilar arteries, although both arteries produced nearly identical maximum contractions.Stroke Vol 16, No 3, 1985 SPECIES DIFFERENCES in the constrictor responses of cerebral arteries to vasoactive agents are of contemporary interest with regard to the pathophysiology of the cerebral circulation. Hardebo, et al 1 reported that histamine was a strong vasoconstrictor in rabbit cerebral arteries but a prominent vasodilator in human cerebral arteries. Norepinephrine is reported to be a much more potent cerebral artery spasmogen in man than in experimental animals such as rats, rabbits or dogs, 1 2 and a potential vasodilator in pig cerebral arteries. 3Postjunctional a-adrenoceptors have recently been subclassified into a,-and a,-type adrenoceptors, based on relative potencies of selective agonists and antagonists.4 " 8 Experiments using such selective agonists and antagonists have suggested that the vasoconstrictor responses of feline middle cerebral artery 9 -l0 and canine basilar artery 2 " to exogenous norepinephrine are predominantly mediated by the a,-adrenoceptor subtype. However, the nature of a,-adrenoceptors in canine cerebral arteries still remains controversial since some discrepancy exists between the experimental results by Sakakibara et al" and those by Toda.2 Sakakibara et al" have reported that an a 2 -agonist clonidine el...

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Section: Discussionsupporting

confidence: 76%

Pharmacological comparison of isolated monkey and dog cerebral arteries.

Sasaki

Kassell

Torner

et al. 1985

Stroke

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“…Neurologic parameters assessed included National Institutes of Health stroke scale score, 30 level of consciousness, orientation, response to commands, visual fields, gaze, pupillary responses, sensory responses, motor function, limb coordination, plantar reflex, presence of neglect, language, and articulation. The patients' baseline, completion of loading dose, and 3 -month neurologic conditions were categorized as normal (stroke scale score of 0) or mild (1-10), moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), or severe (^30) deficit.…”

Section: Methodsmentioning

confidence: 99%

“…In animal studies, naloxone inhibits neutrophiJ superoxide release, 1 alters transmembrane calcium flux, 2 -3 affects lipid peroxidation, 4 has antioxidant actions, 5 stabilizes lysosomal membranes, inhibits proteolysis, 6 and may have several platelet antiaggregatory effects. 7 - 10 Naloxone also blocks the cerebral arterial vasoconstrictive effects of norepinephrine 11 and in high concentrations produces vasodilation and increases cerebral blood flow. 12 Finally, naloxone may attenuate cerebral edema.…”

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confidence: 99%

High-dose intravenous naloxone for the treatment of acute ischemic stroke.

Olinger

Adams

Brott

et al. 1990

Stroke

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To evaluate the safety and possible efficacy of high-dose naloxone for the treatment of acute cerebral ischemia, 38 patients received a loading dose of 160 mg/m 2 over 15 minutes followed by a 24-hour infusion at the rate of 80 mg/m 2 /hr. Nausea and/or vomiting were common side effects. Naloxone was discontinued in seven patients (because of hypotension in one, bradycardia and hypotension in two, myoclonus in one, focal seizures in two, and hypertension in one); all seven patients responded to treatment and no permanent sequelae to naloxone were noted. Twelve of the 38 patients showed early neurologic improvement (by completion of the naloxone loading dose). However, there was no correlation between such a loading dose response and clinical outcome at 3 months. Our experience suggests that naloxone is safe at the dose used, but data for efficacy are inconclusive. (Stroke 1990^21:721-725)

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“…In anaesthetized cats naltrexone produced a decrease in regional cerebral blood flow (rCBF) (Grandison et al, 1982) whereas in anaesthetized dogs (Artru et al, 1980) and unanaesthetized rabbits (Koskinen & Bill, 1983) an effect of naloxone was not observed. Nor was there any effect of naloxone in the in vitro preparation of human pial arteries (Brandt et al, 1983) whereas an inhibition of vasoconstrictor effects of noradrenaline and at a higher concentration a nonspecific vasodilatation of the canine basilar arterial strip was reported by Sasaki et al (1984). In anaesthetized rabbits, TRH caused an increase in rCBF (Koskinen & Bill, 1984) while no effect was observed in the in vitro preparation ofcat cerebral arteries (Hanko et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Effects of raised intracranial pressure on regional cerebral blood flow: a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia

Koskinen¹

1985

British J Pharmacology

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IThe effects on regional cerebral blood flow (rCBF) of raised intracranial pressure (ICP) and of naloxone and thryrotropin releasing hormome (TRH) during this condition were studied in anaesthetized rabbits. 2 The ICP was elevated until a central ischaemic response was observed. The regional blood flow was determined with the microsphere technique before and during elevation of the ICP (ICPe) and after drug treatment.3 Total CBF was reduced by about 70% during ICPe while the uveal blood flow increased slightly and some other peripheral tissue blood flows remained unaffected. 4 The administration of TRH caused an increase in mean arterial blood pressure (MAP) from 11.9 ± 0.6 to 14.6 ± 0.7 kPa and a normalization of the rCBF. In some peripheral tissues, e.g. gastric mucosa and spleen, TRH reduced the blood flow by 53% and 76%, respectively. In blood pressure stabilized animals no effect on rCBF was seen after TRH. 5 Naloxone had no consistent effect on MAP or local blood flow. 6 It was concluded that in the range of cerebral perfusion pressure studied there was a passive relationship between cerebral blood flow and perfusion pressure. The lack ofeffect ofnaloxone and the marked effect of TRH during cerebral ischaemia are consistent with a mechanism of action ofTRH not related to a 'physiological' antagonism of opioids.

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Effects of Naloxone on Canine Cerebral Vascular Smooth Muscle

Cited by 21 publications

References 18 publications

Pharmacological comparison of isolated monkey and dog cerebral arteries.

Pharmacological comparison of isolated monkey and dog cerebral arteries.

High-dose intravenous naloxone for the treatment of acute ischemic stroke.

Effects of raised intracranial pressure on regional cerebral blood flow: a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia

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