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(Hypertension. 2002;39:394.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Upregulation of Arterial Serotonin 1B and 2B Receptors in Deoxycorticosterone Acetate-Salt Hypertension

Amy K.L. Banes; Stephanie W. Watts

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

Reprint requests to Dr Amy Banes, Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg, East Lansing, MI 48824. E-mail banesamy{at}msu.edu

Previous studies have established a role for 5-hydroxytryptamine (5-HT)_2B and 5-HT_1B receptors in mediating enhanced contraction to serotonin (5-HT) in arteries from hypertensive deoxycorticosterone acetate (DOCA)-salt rats. To determine whether the observed increase in responsiveness was due to upregulation of 5-HT receptors, we used Western analysis to measure 5-HT_1B and 5-HT_2B receptor protein density. In endothelium-denuded aortas from hypertensive DOCA-salt rats (mean systolic blood pressure 192±6 mm Hg), 5-HT_1B and 5-HT_2B receptor proteins were upregulated 2-fold compared with the response in the aortas of sham-operated control rats (mean systolic blood pressure 119±2 mm Hg). Contraction to 5-HT_2B receptor agonists was also enhanced in arteries from Wistar-Furth rats given DOCA and salt. This strain is relatively resistant to the hypertensive effects of DOCA and salt treatment. A common factor between the model of DOCA-salt hypertension and the DOCA-salt–treated Wistar-Furth rats is the presence of mineralocorticoids. Therefore, we tested the hypothesis that mineralocorticoids can upregulate 5-HT_1B and 5-HT_2B receptors. Aortas from normal Sprague-Dawley rats were incubated with aldosterone (100 nmol/L) for 8, 12, 24, and 48 hours. The expression of 5-HT_2B and 5-HT_1B receptor proteins was significantly increased (2- fold over vehicle treatment) by 8 hours. 5-HT_2B and 5-HT_1B receptors were upregulated by aldosterone in a concentration-dependent manner, and incubation with spironolactone (10 µmol/L) blocked this upregulation. These data support the conclusion that the increased expression of 5-HT_1B and 5-HT_2B receptors observed in arteries from DOCA-salt rats may be partially due to mineralocorticoids acting via the mineralocorticoid receptor to modulate gene expression.

Key Words: serotonin • aldosterone • arteries • hypertension, sodium-dependent • receptors, serotonin

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