Heterogeneity in 5-HT-induced contractile and proliferative responses in rat pulmonary arterial bed.
OBJECTIVE
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. alpha-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.


CONCLUSIONS
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.
Rodat-Despoix
L
L
INSERM U 885, Laboratoire de Physiologie Cellulaire Respiratoire, Université Bordeaux 2, Bordeaux, France.
Crevel
H
H
Marthan
R
R
Savineau
J-P
JP
Guibert
C
C
D000577:Amides / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011651:Pulmonary Artery / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D000577:Amides; D004791:Enzyme Inhibitors; D008934:Mitogens; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; C108830:Y 27632; D012701:Serotonin; D054460:rho-Associated Kinases