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. 2003 Sep 15:3:12.
doi: 10.1186/1471-2210-3-12. Epub 2003 Sep 15.

Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCA-salt hypertension

Amy K L Banes  1 , Stephanie W Watts
Affiliations

Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCA-salt hypertension

Amy K L Banes et al. BMC Pharmacol. .

Abstract

Background: 5-hydroxytryptamine (5-HT)2B and 5-HT1B receptors are upregulated in arteries from hypertensive DOCA-salt rats and directly by mineralocorticoids. We hypothesized that increased 5-HT2B and 5-HT1B 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-HT2B receptor agonist BW723C86 on day 1; Sham aorta did not contract. The 5-HT1B 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-HT2B receptor levels by day 3; 5-HT1B receptor density was unchanged. Aortic homogenates from the other groups showed unchanged 5-HT2B and 5-HT1B receptor levels.

Conclusion: These data suggest that functional changes of 5-HT2B but not 5-HT1B receptors may play a role in the development of DOCA-salt hypertension.

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Figures

Figure 1
Figure 1
Measurement of fluid consumption by day and treatment group. Vertical bars represent the mean ± sem for the number of animals indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained from day one of treatment.
Figure 2
Figure 2
Measurement of systolic blood pressures. Data are reported in mm Hg. Points represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained from the Sham response on each day . + represents statistically significant difference (p < 0.05) between the response obtained from the day zero measurement from each respective group.
Figure 3
Figure 3
Day 1 A: Effect of the 5-HT2B receptor agonist BW723C86 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. B: Effect of the 5-HT1B receptor agonist CP93129 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. C: Effect of 5-HT in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. Data are reported as a percentage of the initial PE 10-5 M contraction. Points represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the Sham artery.
Figure 4
Figure 4
Day 3 A: Effect of the 5-HT2B receptor agonist BW723C86 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. B: Effect of the 5-HT1B receptor agonist CP93129 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. C: Effect of 5-HT in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. Data are reported as a percentage of the initial PE 10-5 M contraction. Points represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the Sham artery.
Figure 5
Figure 5
Day 5 A: Effect of the 5-HT2B receptor agonist BW723C86 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. B: Effect of the 5-HT1B receptor agonist CP93129 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. C: Effect of 5-HT in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. Data are reported as a percentage of the initial PE 10-5 M contraction. Points represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the Sham artery.
Figure 6
Figure 6
Day 7 A: Effect of the 5-HT2B receptor agonist BW723C86 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. B: Effect of the 5-HT1B receptor agonist CP93129 in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. C: Effect of 5-HT in aorta from Sham-high salt, DOCA-high salt, DOCA-low salt and Sham rats. Data are reported as a percentage of the initial phenylephrine (PE) 10-5 M contraction. Points represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the Sham artery.
Figure 7
Figure 7
Top: Measurement of 5-HT1B receptor protein density in aortic homogenates from Sham, DOCA-low salt, Sham-high salt and DOCA-high salt rats on days 1, 3, 5 and 7. Bottom: Representative western blot probed for the 5-HT1B receptor protein. Units are reported as arbitrary densitometry units. Vertical bars represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the corresponding Sham. Abbreviations: S = Sham; DHS = DOCA-high salt; DLS = DOCA-low salt; SHS = Sham-high salt.
Figure 8
Figure 8
Top: Measurement of 5-HT2B receptor protein density in aortic homogenates from Sham, DOCA-low salt, Sham-high salt and DOCA-high salt rats on days 1, 3, 5 and 7. Bottom: Representative western blot probed for the 5-HT1B receptor protein. Units are reported as arbitrary densitometry units. Vertical bars represent the mean ± sem for the number of experiments indicated in parentheses. * represents statistically significant difference (p < 0.05) between the response obtained in the corresponding Sham. Abbreviations: S = Sham; DHS = DOCA-high salt; DLS = DOCA-low salt; SHS = Sham-high salt.
Figure 9
Figure 9
Systolic blood pressures (SBP), EC50 values and the maximal contraction to 5-HT, BW723C86 and CP93129 represented as a percentage of phenylephrine (10 μM; PE) for Sham, Sham-high salt, DOCA-low salt and DOCA-high salt rats. Values represent the means ± standard error of the mean for each group. The number of animals, data from the data set used for the 5-HT graphs, in each group is indicated in parentheses. * represents statistical difference from response obtained in the Sham.
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