Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man
Introduction Losartan improves stimulated endothelial function in patients with cardiovascular disease, but there are no data to establish whether losartan has this effect in normal man. Furthermore, whether losartan improves basal nitric oxide (NO) activity is controversial. We therefore examined w...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2004-06-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.3317/jraas.2004.015 |
| _version_ | 1797283378091786240 |
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| author | Justein SN Sim Colin Farquharson Allan D Struthers |
| author_facet | Justein SN Sim Colin Farquharson Allan D Struthers |
| author_sort | Justein SN Sim |
| collection | DOAJ |
| description | Introduction Losartan improves stimulated endothelial function in patients with cardiovascular disease, but there are no data to establish whether losartan has this effect in normal man. Furthermore, whether losartan improves basal nitric oxide (NO) activity is controversial. We therefore examined whether treatment with losartan improved basal NO activity in normal, salt-replete man. If so, this would imply that tonic levels of angiotensin II (Ang II) reduce tonic basal levels of NO, even in salt-replete normal man. Methods We performed a randomised, placebo-controlled, double-blind crossover study in 24 healthy volunteers, comparing losartan 50 mg daily for one month versus placebo. Brachial artery endothelial function was assessed by bilateral venous occlusion plethysmography, measuring the response to intra-arterial infusions of the endothelial-dependent and endothelial-independent vasodilators, acetylcholine and sodium nitroprusside respectively and the endothelial-dependent vasoconstrictor N G -monomethyl-L-arginine. Results were analysed by multiple analysis of variance and statistical significance was taken as a p value of ≤ 0.05. Results Losartan significantly increased the vasoconstriction in response to N G -monomethyl-L-arginine (-37 2% vs . -32 +2 %, losartan vs. placebo; p=0.05). Losartan improved the vasodilatation response to acetylcholine; however, this result did not reach significance (214 +2 0% vs. 174 +2 0%, losartan vs. placebo; p=0.15). Losartan did not affect the response to nitroprusside (172 +1 5% vs. 176 +1 6%, losartan vs. placebo; p=0.84). There was no significant difference in blood pressure between the two study days. Conclusions Losartan improves basal NO bioactivity in healthy salt-replete volunteers. Even in salt-replete man, basal Ang II levels exert a tonic effect, which reduces basal NO. |
| first_indexed | 2024-03-07T17:31:00Z |
| format | Article |
| id | doaj.art-5385c15054db4aa9a7f588e8dc36b598 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 |
| language | English |
| last_indexed | 2024-03-07T17:31:00Z |
| publishDate | 2004-06-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-5385c15054db4aa9a7f588e8dc36b5982024-03-02T17:58:44ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32032004-06-01510.3317/jraas.2004.015Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete manJustein SN SimColin FarquharsonAllan D StruthersIntroduction Losartan improves stimulated endothelial function in patients with cardiovascular disease, but there are no data to establish whether losartan has this effect in normal man. Furthermore, whether losartan improves basal nitric oxide (NO) activity is controversial. We therefore examined whether treatment with losartan improved basal NO activity in normal, salt-replete man. If so, this would imply that tonic levels of angiotensin II (Ang II) reduce tonic basal levels of NO, even in salt-replete normal man. Methods We performed a randomised, placebo-controlled, double-blind crossover study in 24 healthy volunteers, comparing losartan 50 mg daily for one month versus placebo. Brachial artery endothelial function was assessed by bilateral venous occlusion plethysmography, measuring the response to intra-arterial infusions of the endothelial-dependent and endothelial-independent vasodilators, acetylcholine and sodium nitroprusside respectively and the endothelial-dependent vasoconstrictor N G -monomethyl-L-arginine. Results were analysed by multiple analysis of variance and statistical significance was taken as a p value of ≤ 0.05. Results Losartan significantly increased the vasoconstriction in response to N G -monomethyl-L-arginine (-37 2% vs . -32 +2 %, losartan vs. placebo; p=0.05). Losartan improved the vasodilatation response to acetylcholine; however, this result did not reach significance (214 +2 0% vs. 174 +2 0%, losartan vs. placebo; p=0.15). Losartan did not affect the response to nitroprusside (172 +1 5% vs. 176 +1 6%, losartan vs. placebo; p=0.84). There was no significant difference in blood pressure between the two study days. Conclusions Losartan improves basal NO bioactivity in healthy salt-replete volunteers. Even in salt-replete man, basal Ang II levels exert a tonic effect, which reduces basal NO.https://doi.org/10.3317/jraas.2004.015 |
| spellingShingle | Justein SN Sim Colin Farquharson Allan D Struthers Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man Journal of the Renin-Angiotensin-Aldosterone System |
| title | Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man |
| title_full | Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man |
| title_fullStr | Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man |
| title_full_unstemmed | Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man |
| title_short | Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man |
| title_sort | tonic levels of angiotensin ii reduce tonic levels of vascular nitric oxide even in salt replete man |
| url | https://doi.org/10.3317/jraas.2004.015 |
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