Heterogeneity in 5-HT-Induced Contractile and Proliferative Responses in Rat Pulmonary Arterial Bed

Abstract

Aims: 5-Hydroxytryptamine (5-HT) is a potent vasoconstrictor and mitogen in the pulmonary vascular bed which exhibits phenotypical and functional heterogeneity according to size of the vessels. Methods: We thus investigated both contractile response and smooth muscle cell (SMC) proliferation in response to 5-HT in rat main extrapulmonary artery (MPA) and intrapulmonary arteries of the first and second order (IPA1 and IPA2). Results: The contractile effect of 5-HT was higher in IPA1 and IPA2 compared to MPA. 5-HT₂ receptor antagonists like ketanserin and ritanserin and a 5-HT_1B/D receptor antagonist, GR127935, partially inhibited the contraction. α-Methyl-5-HT, a 5-HT₂ receptor agonist, induced a higher contraction in MPA than in IPA and inversely 5-carboxamidotryptamine, a 5-HT₁ receptor agonist, induced a higher contraction in IPA2 than in MPA and IPA1. Nitrendipine reduced the contraction, whereas the addition of thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca-ATPases, had an additive blocking effect only in IPA1. The residual contraction to 5-HT was abolished by Y-27632, a rho kinase inhibitor. Finally, SMC proliferation in response to 5-HT was higher in MPA than in IPA2. Conclusion: Our results demonstrate regional differences in SMC proliferation as well as in the functional role of 5-HT receptors and the sarcoplasmic reticulum in the contraction.