DOI: 10.1161/01.str.26.6.1079. Cerebral Blood Flow During Inhibition of Brain Nitric Oxide Synthase Activity in Normal, Hypertensive, and Stroke-Prone Rats

Cerebral Blood Flow During Inhibition of Brain Nitric Oxide Synthase Activity in Normal, Hypertensive, and Stroke-Prone Rats

10.1161/01.str.26.6.1079

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

Background and Purpose Because tonic production of nitric oxide (NO) is important in regulating cerebrovascular tone and NO may be important in the mechanism of brain injury from focal ischemia, we speculated that stroke predisposition in spontaneously hypertensive stroke-prone rats (SHR-SP) may be related to impaired tonic production of NO. This study was designed to test the hypothesis that the cerebral blood flow (CBF) response to inhibition of NO synthase in SHR-SP would be different than that observed in normal Wistar-Kyoto (WKY) rats and non–stroke-prone spontaneously hypertensive rats (SHR). Methods Pentobarbital-anesthetized, mechanically ventilated rats were tested for CBF response to saline, 5 or 20 mg/kg IV of N G -monomethyl- l -arginine (L-NMMA), or 20 mg/kg IV of N ω -nitro- l -arginine (L-NA). In addition, specificity for an NO-dependent mechanism was assessed by determining the ability to reverse any alteration in CBF with l -arginine. Hemorrhage was used to minimize any increase in mean arterial blood pressure (MABP) from NO synthase inhibition. In a separate cohort of rats, differential sensitivity of NO synthase for inhibition by nitro-arginine analogues was determined. Results Baseline MABP was greater in SHR-SP (185±3, n=38) and SHR (169±3, n=38) compared with WKY rats (101±2 mm Hg, n=38, P <.05). Baseline CBF was similar between strains; however, cerebrovascular resistance was higher in SHR-SP (2.16±0.09, n=27) and SHR (1.94±0.07, n=27) compared with WKY rats (1.23±0.06 mm Hg/mL per minute per 100 g, n=27, P <.05). CBF was unchanged with 5 mg/kg L-NMMA or with l -arginine in the absence of L-NMMA in each strain. CBF decreased similarly in SHR and SHR-SP (n=9 each) in response to 20 mg/kg L-NMMA (SHR, 85±6 to 67±6; SHR-SP, 87±7 to 69±5 mL/min per 100 g) and was completely reversed by l -arginine. CBF did not decrease with 20 mg/kg L-NMMA in WKY rats. Administration of L-NA (n=5 each) produced similar reduction of CBF (WKY rats, 67±6%; SHR, 49±9%; SHR-SP, 61±6% of baseline) and inhibition of NO synthase in each strain (≈80% inhibition). Conclusions There was no difference in the cerebrovascular response to NO synthase inhibition in SHR-SP and non–stroke-prone SHR. Therefore, it is unlikely that an altered sensitivity of NO synthase to inhibition can explain predisposition to stroke in SHR-SP.

Bibliography

Izuta, M., Clavier, N., Kirsch, J. R., & Traystman, R. J. (1995). Cerebral Blood Flow During Inhibition of Brain Nitric Oxide Synthase Activity in Normal, Hypertensive, and Stroke-Prone Rats. Stroke, 26(6), 1079â1085.

Authors 4

Makoto Izuta (first)
Nathalie Clavier (additional)
Jeffrey R. Kirsch (additional)
Richard J. Traystman (additional)

References 41 Referenced 20

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Ichord RN, Helfaer MA, Kirsch JR, Wilson D, Traystman RJ. Nitric oxide synthase inhibition attenuates hypoglycemic cerebral hyperemia in piglets. Am J Physiol. 1994;266:H1062-H1068. / Am J Physiol (1994)
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Mayhan WG, Faraci FM, Heistad DD. Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension. Am J Physiol. 1987;253:H1435-H1440. / Am J Physiol (1987)
Mayhan WG. Role of prostaglandin H2-thromboxane A2 in responses of cerebral arterioles during chronic hypertension. Am J Physiol. 1992;262:H539-H543. / Am J Physiol (1992)
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Dietrich HH, Kimura M, Dacey RGJ. Nw-Nitro-L-arginine constricts cerebral arterioles without increasing intracellular calcium levels. Am J Physiol. 1994;266:H1681-H1686. / Am J Physiol (1994)
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Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 6:32 p.m.)
Indexed	2 months, 2 weeks ago (June 12, 2025, 5:27 a.m.)
Issued	30 years, 3 months ago (June 1, 1995)
Published	30 years, 3 months ago (June 1, 1995)
Published Print	30 years, 3 months ago (June 1, 1995)

Funders 0

None

BibTeX

@article{Izuta_1995, title={Cerebral Blood Flow During Inhibition of Brain Nitric Oxide Synthase Activity in Normal, Hypertensive, and Stroke-Prone Rats}, volume={26}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.26.6.1079}, DOI={10.1161/01.str.26.6.1079}, number={6}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Izuta, Makoto and Clavier, Nathalie and Kirsch, Jeffrey R. and Traystman, Richard J.}, year={1995}, month=jun, pages={1079–1085} }

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  "abstract": "<jats:p>\n            <jats:italic>Background and Purpose</jats:italic>\n            Because tonic production of nitric oxide (NO) is important in regulating cerebrovascular tone and NO may be important in the mechanism of brain injury from focal ischemia, we speculated that stroke predisposition in spontaneously hypertensive stroke-prone rats (SHR-SP) may be related to impaired tonic production of NO. This study was designed to test the hypothesis that the cerebral blood flow (CBF) response to inhibition of NO synthase in SHR-SP would be different than that observed in normal Wistar-Kyoto (WKY) rats and non\u2013stroke-prone spontaneously hypertensive rats (SHR).\n          </jats:p>\n          <jats:p>\n            <jats:italic>Methods</jats:italic>\n            Pentobarbital-anesthetized, mechanically ventilated rats were tested for CBF response to saline, 5 or 20 mg/kg IV of\n            <jats:italic>N</jats:italic>\n            <jats:sup>G</jats:sup>\n            -monomethyl-\n            <jats:sc>l</jats:sc>\n            -arginine (L-NMMA), or 20 mg/kg IV of\n            <jats:italic>N</jats:italic>\n            <jats:sup>\u03c9</jats:sup>\n            -nitro-\n            <jats:sc>l</jats:sc>\n            -arginine (L-NA). In addition, specificity for an NO-dependent mechanism was assessed by determining the ability to reverse any alteration in CBF with\n            <jats:sc>l</jats:sc>\n            -arginine. Hemorrhage was used to minimize any increase in mean arterial blood pressure (MABP) from NO synthase inhibition. In a separate cohort of rats, differential sensitivity of NO synthase for inhibition by nitro-arginine analogues was determined.\n          </jats:p>\n          <jats:p>\n            <jats:italic>Results</jats:italic>\n            Baseline MABP was greater in SHR-SP (185\u00b13, n=38) and SHR (169\u00b13, n=38) compared with WKY rats (101\u00b12 mm Hg, n=38,\n            <jats:italic>P</jats:italic>\n            &lt;.05). Baseline CBF was similar between strains; however, cerebrovascular resistance was higher in SHR-SP (2.16\u00b10.09, n=27) and SHR (1.94\u00b10.07, n=27) compared with WKY rats (1.23\u00b10.06 mm Hg/mL per minute per 100 g, n=27,\n            <jats:italic>P</jats:italic>\n            &lt;.05). CBF was unchanged with  5 mg/kg L-NMMA or with\n            <jats:sc>l</jats:sc>\n            -arginine in the absence of L-NMMA in each strain. CBF decreased similarly in SHR and SHR-SP (n=9 each) in response to 20 mg/kg L-NMMA (SHR, 85\u00b16 to 67\u00b16; SHR-SP, 87\u00b17 to 69\u00b15 mL/min per 100 g) and was completely reversed by\n            <jats:sc>l</jats:sc>\n            -arginine. CBF did not decrease with 20 mg/kg L-NMMA in WKY rats. Administration of L-NA (n=5 each) produced similar reduction of CBF (WKY rats, 67\u00b16%; SHR, 49\u00b19%; SHR-SP, 61\u00b16% of baseline) and inhibition of NO synthase in each strain (\u224880% inhibition).\n          </jats:p>\n          <jats:p>\n            <jats:italic>Conclusions</jats:italic>\n            There was no difference in the cerebrovascular response to NO synthase inhibition in SHR-SP and non\u2013stroke-prone SHR. Therefore, it is unlikely that an altered sensitivity of NO synthase to inhibition can explain predisposition to stroke in SHR-SP.\n          </jats:p>",
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