Effects of halothane and urethane-chloralose anaesthesia on the pressor and cerebrovascular responses to 7-nitroindazole, an inhibitor of nitric oxide synthase

Yuri Zagvazdin, Giuseppe Sancesario, Malinda E.C. Fitzgerald, Anton Reiner

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We examined the effect of 7-nitroindazole (7NI), a reportedly relatively specific inhibitor of the neuronal isoform of nitric oxide synthase (nNOS), on mean arterial blood pressure and on cerebral blood flow in rats under three different types of anaesthesia: urethane-chloralose, halothane, or urethane preceded by induction of anaesthesia with halothane. In rats under urethane-chloralose anaesthesia, 7NI induced an increase in mean systemic arterial blood pressure. In contrast, halothane used for induction and maintenance of anaesthesia eliminated the 7NI-induced systemic pressor effect, while halothane used only for induction of anaesthesia greatly attenuated the 7NI-induced systemic pressor effect. Cerebral blood flow, as measured by Laser Doppler flowmetry, decreased significantly to 85-72% of baseline within 5-10 min after i.p. 7NI injection regardless of the type of anaesthesia. Blockade of the systemic pressor effect of 7NI by halothane but not of the reduction in cerebral blood flow produced by 7NI is consistent with prior evidence that: (1) the cerebral vasculature and the peripheral vasculature differ in the isoforms of NOS involved in maintaining vascular tone, with nNOS more important in the former and endothelial NOS (eNOS) in the latter; and (2) halothane interferes with eNOS-mediated vascular tone but not nNOS-mediated control of cerebral blood flow. The fact that 7NI yields a pressor effect that can be attenuated by halothane, as also true for isoform-non-selective NOS inhibitors, raises the possibility that 7NI may to some extent inhibit endothelial NO formation.

Original languageEnglish (US)
Pages (from-to)339-346
Number of pages8
JournalPharmacological Research
Volume38
Issue number5
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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Chloralose
Urethane
Halothane
Nitric Oxide Synthase
Anesthesia
Cerebrovascular Circulation
Protein Isoforms
Nitric Oxide Synthase Type I
Arterial Pressure
Blood Vessels
7-nitroindazole
Laser-Doppler Flowmetry
Maintenance
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Effects of halothane and urethane-chloralose anaesthesia on the pressor and cerebrovascular responses to 7-nitroindazole, an inhibitor of nitric oxide synthase. / Zagvazdin, Yuri; Sancesario, Giuseppe; Fitzgerald, Malinda E.C.; Reiner, Anton.

In: Pharmacological Research, Vol. 38, No. 5, 01.01.1998, p. 339-346.

Research output: Contribution to journalArticle

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abstract = "We examined the effect of 7-nitroindazole (7NI), a reportedly relatively specific inhibitor of the neuronal isoform of nitric oxide synthase (nNOS), on mean arterial blood pressure and on cerebral blood flow in rats under three different types of anaesthesia: urethane-chloralose, halothane, or urethane preceded by induction of anaesthesia with halothane. In rats under urethane-chloralose anaesthesia, 7NI induced an increase in mean systemic arterial blood pressure. In contrast, halothane used for induction and maintenance of anaesthesia eliminated the 7NI-induced systemic pressor effect, while halothane used only for induction of anaesthesia greatly attenuated the 7NI-induced systemic pressor effect. Cerebral blood flow, as measured by Laser Doppler flowmetry, decreased significantly to 85-72{\%} of baseline within 5-10 min after i.p. 7NI injection regardless of the type of anaesthesia. Blockade of the systemic pressor effect of 7NI by halothane but not of the reduction in cerebral blood flow produced by 7NI is consistent with prior evidence that: (1) the cerebral vasculature and the peripheral vasculature differ in the isoforms of NOS involved in maintaining vascular tone, with nNOS more important in the former and endothelial NOS (eNOS) in the latter; and (2) halothane interferes with eNOS-mediated vascular tone but not nNOS-mediated control of cerebral blood flow. The fact that 7NI yields a pressor effect that can be attenuated by halothane, as also true for isoform-non-selective NOS inhibitors, raises the possibility that 7NI may to some extent inhibit endothelial NO formation.",
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