Endothelium-derived nitric oxide synthase inhibition. Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats.

Prado, Ricardo; Watson, Brant D.; Kuluz, John W.; Dietrich, W. Dalton

doi:10.1161/01.str.23.8.1118

Cited by 126 publications

(43 citation statements)

References 33 publications

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“…However, it may be noted that under pentobarbitone anaesthesia, capillary blood flow is approximately one-third of the total carotid blood flow (Saxena & Verdouw, 1982;1985;Den Boer et al, 1992;present results) and thus the basal release of NO may already be too low to detect a significant decrease. In contrast to a number of studies which reported a moderate reduction in cerebral blood flow following NOsynthase inhibition, suggesting a basal NO-release in this part of the cranial circulation (Kovaich et al, 1992;Prado et al, 1992;Seligsohn & Bill, 1993), in our present experiments L-NAME failed to reduce the cerebral component of carotid blood flow. The absence of an endothelial NO-dependent dilator tone is supported by the recent finding that cultured rat brain microvessel endothelial cells do not show basal release of NO (Durieu-Trautmann et al, 1993).…”

Section: Regional Carotid Bloodflowcontrasting

confidence: 99%

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig

Gelderen

Saxena

1994

British J Pharmacology

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1 The role of nitric oxide (NO) biosynthesis in the regulation of blood flow through arteriovenous anastomoses was evaluated in the carotid circulation of the anaesthetized pig. For this purpose, the effect of intracarotid (i.c.) administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 0.3 and 1.0 mg kg-'; n = 6) or saline (n = 6) was studied on the distribution of common carotid blood flow, using the radioactive microsphere method. 2 Apart from the highest dose, L-NAME caused no major changes in the systemic haemodynamic variables. Both cardiac output and systemic vascular conductance were reduced by L-NAME (1 mg kg-'), being reversed partly by L-arginine (100 mg kg-', i.c.). In both groups, L-arginine slightly reduced mean arterial blood pressure. 3 Total common carotid artery blood flow as well as its distribution over the capillary and arteriovenous anastomotic fraction remained stable after saline injection. In contrast, L-NAME caused a dose-dependent decline in common carotid artery blood flow and conductance and this decline was confined entirely to its arteriovenous anastomotic part. 4 Subsequent intracarotid injection of L-arginine (100mg kg-') reversed the reduction in total carotid conductance almost completely and that in the arteriovenous anastomotic region partially. Additionally, L-arginine increased capillary conductance significantly in the L-NAME -as well as the saline-treated animals. 5 These results indicate that the L-arginine-NO pathway contributes little to the regulation of tissue perfusion in the porcine carotid circulation. In contrast, NO seems to play an important role in shunting arterial blood through arteriovenous anastomoses in the anaesthetized pig. Keywords: Arteriovenous anastomoses; endothelium; N0-nitro-L-arginine methyl ester; nitric oxide; nitrite; blood flow in pig IntroductionArteriovenous anastomoses have been found in animals and man, although their precise physiological function is not yet fully understood. Cutaneous arteriovenous anastomoses may be implicated in the regulation of the body temperature and blood pressure (Hales & Molyneux, 1988). Furthermore, dilatation of cranial arteriovenous anastomoses has been proposed to contribute to the pathogenesis of migraine headache (Heyck, 1969;Saxena, 1978;1990).Little is known of the mechanisms involved in opening arteriovenous anastomoses, which are normally under a constrictor tone. However, for several reasons nitric oxide (NO), which is formed from L-arginine by the calcium/calmodulin dependent enzyme NO-synthase (Palmer et al., 1988; Fdrstermann et al., 1991), may be a potential candidate: (i) as indicated by the inhibition of NO biosynthesis using NW-nitro-L-arginine methyl ester (L-NAME), continuous production of NO apparently contributes to the regulation of arterial blood pressure and tissue perfusion (Gardiner et al., 1990;Rees et al., 1990;Van Gelderen et al., 1991); (ii) compounds that act via the NO system (e.g. nit-roglycerin, isosorbide mononitrate) cause headache as wel...

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Section: Regional Carotid Bloodflowcontrasting

confidence: 99%

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig

Gelderen

Saxena

1994

British J Pharmacology

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“…Finally, it has been shown that NO can increase cerebral blood flow (Prado et al, 1992) by releasing vascular smooth muscle cells (Moncada et al, 1991). Therefore, the microiontophoretic application of SNOG or L-NAME could influence the microvascular tone by interfering with NO formation.…”

Section: Possible Mechanisms Involved In the No-dependent Modulation mentioning

confidence: 99%

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

et al. 2011

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Aim: The effects of local applied NO-active compounds on glutamate (GLU)-evoked responses were investigated in globus pallidus (GP) neurons. Main methods: Extracellularly recorded single units from anesthetized rats were treated with GLU before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-Larginine methyl ester (L-NAME), a NOS inhibitor. Key findings: Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their excitatory responses to the administration of iontophoretic GLU. In these cells, the changes induced by NO-active drugs in the magnitude of GLU-evoked responses were used as indicators of NO modulation. In fact, when a NO-active drug was co-iontophoresed with GLU, significant changes in GLU-induced responses were observed: generally, increased magnitudes of GLU-evoked responses were observed during SNOG ejection, whereas the administration of L-NAME decreased responses to GLU. Significance: The results suggest that the NO-active drugs modulate the response of GP neurons to glutamatergic transmission. Nitrergic modulation of glutamatergic transmission could play an important role in the control of GP bioelectric activity, considered a fundamental key in the BG function.

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“…In deeper cerebral tissue, however, such a contribution may be of functional importance (Tanaka et al, 1991;Pellegrino et al, 1992). Others find this to be valid also in cortical vessels (Faraci, 1991; Tanaka et al, 1991;Prado et al, 1992). Such discrepancies may at least partly result from meth odological differences.…”

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confidence: 95%

Inhibition of Nitric Oxide Synthase Attenuates the Cerebral Blood Flow Response to Stimulation of Postganglionic Parasympathetic Nerves in the Rat

Morita-Tsuzuki

Hardebo

Bouskela

1993

J Cereb Blood Flow Metab

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Summary: Stimulation of cerebrovascular parasympa thetic nerves markedly increases cortical blood flow. Ni tric oxide (NO) or a NO-containing compound is present in these nerves and may therefore, upon release, be partly responsible for the flow increase. In addition, transmit ters released from the nerves may cause synthesis and release of this compound from the endothelium. The contribution of NO synthesis to the cortical blood flow (CoBF) increase during parasympathetic stimulation was elucidated in rat by laser-Doppler flowmetry.Thirty-minute exposure to circulating N w -nitro-L-arginine methyl ester (L-NAME) 50 mg kg-1 eliminated most of the response (from 104 to 8% increase), whereas lO-min The pial arterial tree is innervated by a network of parasympathetic fibers (for review see U ddman and Edvinsson, 1989;Suzuki and Hardebo, 1993). Some of these fibers may extend along branches into the brain parenchyma. Stimulation of the para sympathetic fibers markedly increases the cortical blood flow (CoB F) (see Suzuki and Hardebo, 1993). Upon activation, these fibers may modulate cere bral autoregulation (Koketsu et aI. , 1992; Morita Tsuzuki et aI. , 1993) and suppress infarction volume following cerebral artery occlusion (Kano et aI., 1991; Koketsu et aI., 1992).Acetylcholine, present as transmitter in parasym pathetic nerves (Suzuki et aI. , 1990a), exerts its whole vasodilator action through a release of endoReceived December 16, 1992; final revision received April 12, 1993; accepted May 3, 1993 Address correspondence and reprint requests to Dr. Y. Morita-Tsuzuki at Department of Neurology, Second Tokyo Na tional Hospital, 2-5-Higashigaoka, Meguro-ku, Tokyo 152, Ja pan.Abbreviations used: CoBF, cortical blood flow; MCA, middle cerebral artery; L-NAME, Nw-nitro-L-arginine methyl ester. 993exposure to this dose or 30-min exposure to 5 mg kg -1 caused a less marked reduction. The reducing effect was particularly evident after elimination of the systemic blood pressure increase caused by L-NAME (only 3% increase after the high dose). Infusion of L-arginine re stored the flow response. Resting CoBF was not substan tially affected by blockade of NO formation. Thus, re lease of an NO-containing compound constitutes a major component of the increase in CoBF caused by parasym pathetic nerve stimulation but does not seem to contrib ute to cortical flow regulation during resting conditions.

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Endothelium-derived nitric oxide synthase inhibition. Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats.

Abstract: Background and Purpose:We determined the effects of inhibiting the production of cerebral endothelium-derived nitric oxide on pial artery diameter, cortical blood flow, and vascular morphology.Methods: An inhibitor of endothelium-derived nitric oxide synthesis, JV

Cited by 126 publications

References 33 publications

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

Inhibition of Nitric Oxide Synthase Attenuates the Cerebral Blood Flow Response to Stimulation of Postganglionic Parasympathetic Nerves in the Rat

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