Upregulation of arterial serotonin 1B and 2B receptors in deoxycorticosterone acetate-salt hypertension

Previous studies have established a role for 5-hydroxytryptamine (5-HT)(2B) and 5-HT1B 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-HT1B and 5-HT2B receptor protein density. In endothelium-denuded aortas from hypertensive DOCA-salt rats (mean systolic blood pressure 192+/-6 mm Hg), 5-HT1B and 5-HT2B receptor proteins were upregulated approximate to2-fold compared with the response in the aortas of sham-operated control rats (mean systolic blood pressure 119+/-2 mm Hg). Contraction to 5-HT2B 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-HT1B and 5-HT2B 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-HT2B and 5-HT1B receptor proteins was significantly increased (approximate to2- fold over vehicle treatment) by 8 hours. 5-HT2B and 5-HT1B receptors were upregulated by aldosterone in a concentration-dependent manner. and incubation with spironolactone (10 mumol/L) blocked this upregulation. These data support the conclusion that the increased expression of 5-HT1B and 5-HT2B receptors observed in arteries from DOCA-salt rats may be partially due to mineralocorticoids acting via the mineralocorticoid receptor to modulate gene expression.