Arterial expression of 5-HT(2B )and 5-HT(1B )receptors during development of DOCA-salt hypertension

BACKGROUND: 5-hydroxytryptamine (5-HT)(2B )and 5-HT(1B )receptors are upregulated in arteries from hypertensive DOCA-salt rats and directly by mineralocorticoids. We hypothesized that increased 5-HT(2B )and 5-HT(1B )receptor density and contractile function would precede increased blood pressure in DOCA-high salt rats. We performed DOCA-salt time course (days 1, 3, 5 and 7) studies using treatment groups of: DOCA-high salt, DOCA-low salt, Sham and Sham-high salt rats. RESULTS: In isolated-tissue baths, DOCA-high salt aorta contracted to the 5-HT(2B )receptor agonist BW723C86 on day 1; Sham aorta did not contract. The 5-HT(1B )receptor agonist CP93129 had no effect in arteries from any group. On days 3, 5 and 7 CP93129 and BW723C86 contracted DOCA-high salt and Sham-high salt aorta; Sham and DOCA-low salt aorta did not respond. Western analysis of DOCA-high salt aortic homogenates revealed increased 5-HT(2B )receptor levels by day 3; 5-HT(1B )receptor density was unchanged. Aortic homogenates from the other groups showed unchanged 5-HT(2B )and 5-HT(1B )receptor levels. CONCLUSION: These data suggest that functional changes of 5-HT(2B )but not 5-HT(1B )receptors may play a role in the development of DOCA-salt hypertension.