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Research ArticleCARDIOVASCULAR

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Jessica Diaz, Wei Ni, Janice Thompson, Andrew King, Gregory D. Fink and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics June 2008, 325 (3) 1031-1038; DOI: https://doi.org/10.1124/jpet.108.136226
Jessica Diaz
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Wei Ni
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Janice Thompson
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Andrew King
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Gregory D. Fink
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Stephanie W. Watts
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Abstract

Arterial hyper-responsiveness to 5-hydroxytryptamine (5-HT) is a hallmark of hypertension, and plasma levels of free 5-HT are elevated in hypertension. We hypothesized that chronic administration of 5-HT would cause blood pressure to 1) rise in normotensive rats and 2) rise significantly more in hypertensive rats. The deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rat were used. Animals were implanted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 μg/kg/min for 7 days. Free plasma 5-HT was elevated significantly by this protocol. Within 48 h, mean arterial blood pressure measured telemetrically decreased in sham (106 ± 2 to 83 ± 2 mm Hg) and in DOCA-salt hypertensive (166 ± 9 to 112 ± 3 mm Hg) rats; vehicle did not change blood pressure in either group. Ganglionic blockade (hexamethonium) reduced blood pressure to a greater magnitude in DOCA vehicle-administered rats (peak fall arterial pressure, 91 ± 14 mm Hg) compared with DOCA 5-HT-administered rats (40 ± 6 mm Hg). Maximal acetylcholine-induced (NO-dependent) relaxation in phenylephrine-contracted aortic strips was greater in 5-HT-administered (69.2 ± 9.1% relaxation) versus vehicle-administered (39.7 ± 14.2%) DOCA rats; aortic endothelial cell nitric oxide synthase expression was higher in the 5-HT- versus vehicle-administered DOCA-salt rats. In normotensive and DOCA-salt hypertensive rats, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine (0.5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS.

Footnotes

  • This study was supported by the National Institutes of Health Grant HL81115.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.108.136226.

  • ABBREVIATIONS: 5-HT, 5-hydroxytryptamine; SERT, serotonin transporter; 5-HIAA, 5-hydroxyindole acetic acid; DOCA, deoxycorticosterone acetate; LNNA, Nω-nitro-l-arginine; PRP, platelet-rich plasma; PPP, platelet-poor plasma; ACh, acetylcholine; eNOS, endothelial cell nitric oxide synthase; NOS, nitric oxide synthase; PE, phenylephrine.

    • Received January 4, 2008.
    • Accepted February 26, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 368 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 368, Issue 3
1 Mar 2019
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Research ArticleCARDIOVASCULAR

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Jessica Diaz, Wei Ni, Janice Thompson, Andrew King, Gregory D. Fink and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics June 1, 2008, 325 (3) 1031-1038; DOI: https://doi.org/10.1124/jpet.108.136226

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Research ArticleCARDIOVASCULAR

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Jessica Diaz, Wei Ni, Janice Thompson, Andrew King, Gregory D. Fink and Stephanie W. Watts
Journal of Pharmacology and Experimental Therapeutics June 1, 2008, 325 (3) 1031-1038; DOI: https://doi.org/10.1124/jpet.108.136226
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