nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure.
We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant aden...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797097836578340864 |
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| author | Wang, Y Patel, K Cornish, K Channon, K Zucker, I |
| author_facet | Wang, Y Patel, K Cornish, K Channon, K Zucker, I |
| author_sort | Wang, Y |
| collection | OXFORD |
| description | We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.beta-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 +/- 0.3 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 3.8 +/- 0.3 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 +/- 19 vs. 94 +/- 12 beats/min, P < 0.05 and 130 +/- 16 vs. 106 +/- 5% max/mmHg, P < 0.05) compared with the Ad.beta-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 +/- 0.2 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 2.6 +/- 0.2 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.beta-Gal gene transfer (188 +/- 15 vs. 127 +/- 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF. |
| first_indexed | 2024-03-07T05:00:58Z |
| format | Journal article |
| id | oxford-uuid:d8456914-9caf-4f53-83d4-c46e66944ad4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:00:58Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:d8456914-9caf-4f53-83d4-c46e66944ad42022-03-27T08:47:05ZnNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d8456914-9caf-4f53-83d4-c46e66944ad4EnglishSymplectic Elements at Oxford2003Wang, YPatel, KCornish, KChannon, KZucker, IWe hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.beta-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 +/- 0.3 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 3.8 +/- 0.3 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 +/- 19 vs. 94 +/- 12 beats/min, P < 0.05 and 130 +/- 16 vs. 106 +/- 5% max/mmHg, P < 0.05) compared with the Ad.beta-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 +/- 0.2 vs. 0.8 +/- 0.2 beats.min-1.mmHg-1, P < 0.01 and 2.6 +/- 0.2 vs. 1.2 +/- 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.beta-Gal gene transfer (188 +/- 15 vs. 127 +/- 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF. |
| spellingShingle | Wang, Y Patel, K Cornish, K Channon, K Zucker, I nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title | nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title_full | nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title_fullStr | nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title_full_unstemmed | nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title_short | nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. |
| title_sort | nnos gene transfer to rvlm improves baroreflex function in rats with chronic heart failure |
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