Blood pressure in healthy humans is regulated by neuronal NO synthase
NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effect...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Heart Association
2017
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| _version_ | 1826268581674876928 |
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| author | Shabeeh, H Khan, S Jiang, B Brett, S Melikian, N Casadei, B Chowienczyk, P Shah, A |
| author_facet | Shabeeh, H Khan, S Jiang, B Brett, S Melikian, N Casadei, B Chowienczyk, P Shah, A |
| author_sort | Shabeeh, H |
| collection | OXFORD |
| description | NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1–3.0 µmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 µmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P<0.01). There were significant decreases in heart rate (60±4 to 51±3 bpm; P<0.01) and left ventricular stroke volume (59±6 to 51±6 mL; P<0.01) but ejection fraction was unaltered. S-methyl-l-thiocitrulline had no effect on radial artery flow-mediated dilatation, an index of endothelial NOS activity. These results suggest that nNOS-derived NO has an important role in the physiological regulation of basal systemic vascular resistance and blood pressure in healthy humans. |
| first_indexed | 2024-03-06T21:11:53Z |
| format | Journal article |
| id | oxford-uuid:3e770bb7-6192-4238-a6d6-0226a781f162 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:11:53Z |
| publishDate | 2017 |
| publisher | American Heart Association |
| record_format | dspace |
| spelling | oxford-uuid:3e770bb7-6192-4238-a6d6-0226a781f1622022-03-26T14:25:38ZBlood pressure in healthy humans is regulated by neuronal NO synthaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e770bb7-6192-4238-a6d6-0226a781f162EnglishSymplectic Elements at OxfordAmerican Heart Association2017Shabeeh, HKhan, SJiang, BBrett, SMelikian, NCasadei, BChowienczyk, PShah, ANO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1–3.0 µmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 µmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P<0.01). There were significant decreases in heart rate (60±4 to 51±3 bpm; P<0.01) and left ventricular stroke volume (59±6 to 51±6 mL; P<0.01) but ejection fraction was unaltered. S-methyl-l-thiocitrulline had no effect on radial artery flow-mediated dilatation, an index of endothelial NOS activity. These results suggest that nNOS-derived NO has an important role in the physiological regulation of basal systemic vascular resistance and blood pressure in healthy humans. |
| spellingShingle | Shabeeh, H Khan, S Jiang, B Brett, S Melikian, N Casadei, B Chowienczyk, P Shah, A Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title | Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title_full | Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title_fullStr | Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title_full_unstemmed | Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title_short | Blood pressure in healthy humans is regulated by neuronal NO synthase |
| title_sort | blood pressure in healthy humans is regulated by neuronal no synthase |
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