title: Upregulation of arterial serotonin 1B and 2B receptors in deoxycorticosterone acetate-salt hypertension.
abstract: 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 approximately 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 (approximately 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 micromol/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.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA. banesamy@msu.edu
authors.forename: Amy K L
authors.initials: AK
authors.lastname: Banes
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008901:Mineralocorticoids; D044302:Receptor, Serotonin, 5-HT1B; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D003900:Desoxycorticosterone; D000450:Aldosterone