Plasma serotonin levels are normal in pulmonary arterial hypertension☆
Introduction
Serotonin (5-HT) is a potent pulmonary vasoconstrictor and platelet aggregator that has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). Most human circulating 5-HT is stored in platelets, while only platelet-free plasma 5-HT has potent vascular activity. Two previous studies (N=16 each) have shown increased plasma 5-HT levels in patients with idiopathic PAH (IPAH) [1], [2]. In addition, a 5-HT promoter polymorphism has been associated with the risk of PAH in one population, although this association was not seen in other populations [3], [4], [5]. We therefore hypothesized that plasma 5-HT levels would be significantly elevated in PAH related to associated conditions (APAH).
Section snippets
Methods
We performed a prospective cohort study of patients with PAH undergoing initial right heart catheterization at our center beginning in November 2001. We excluded patients already receiving targeted PAH treatment. We also included age- and gender-matched healthy controls. The Columbia University Institutional Review Board approved the study.
A bionutritionist counseled subjects to avoid 5-HT-rich foods, alcohol and coffee for 48 h before phlebotomy; subjects recorded foods eaten during this
Results
We enrolled 28 PAH patients and 8 controls; 21 patients and 6 controls were compliant with dietary restrictions and comprised the final study sample (Table 1). Two PAH patients had collagen vascular disease, 3 had HIV, 5 had congenital cardiac shunts (2 repaired), 6 had portopulmonary hypertension, and 5 had IPAH.
Patients with APAH did not have elevated plasma 5-HT levels compared to controls (Fig. 1; p=0.51). Patients with IPAH also had 5-HT levels similar to those of controls. In fact, only 1
Discussion
We found that patients with APAH and IPAH had plasma 5-HT levels that were similar to those of healthy controls. These results differ from those of previous studies in which PAH was associated with dramatically higher 5-HT levels (>30 nmol/L) [1], [2]. There are a number of possible explanations for these discrepant findings.
First, we specifically focused on patients with APAH, whereas prior studies predominantly included patients with IPAH. Of note, however, 5-HT levels were also normal in
Acknowledgments
The authors wish to thank May Huang, M.S. and the staff of the Irving Center for Clinical Research at Columbia University for their assistance with this study.
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Funded by NIH HL67771, HL072739, HL082895, and RR00645.