Copyright (C) 2007 S. Karger AG, Basel.”
“Aims: 5-Hydroxytryptamine (5-HT) is a potent vasoconstrictor Nirogacestat manufacturer 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-HT1B/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 EPZ-6438 clinical trial 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. Copyright (C) 2007 S. Karger AG, Basel.”
“Although most physiologically important processes are regulated through negative feedback loops and numerous factors regulating endothelial apoptosis are identified, little is known about negative feedback mechanisms for endothelial Plasmin apoptosis.

Here we describe the release of soluble antiapoptotic activity by endothelial cells undergoing apoptosis, and identify fibroblast growth factor-2 (FGF-2) as contributing to this. In brief, apoptosis of human umbilical vein endothelial cells was induced by serum deprivation and confirmed by transmission electron microscopy, DNA gel electrophoresis and a sub-diploid population seen by fluorescence-activated cell scanning analysis. Apoptosis was most rapid early during culture, and this was demonstrated to be due to the accumulation of soluble anti-apoptotic activity in experiments replacing culture medium with fresh medium, or alternatively returning conditioned medium to cells. FGF-2 antigen was detected in both conditioned medium and cell lysates, while neutralizing antibodies reduced the protective effect of medium conditioned by apoptotic endothelium. Experiments with the highly specific FGF-2 receptor tyrosine kinase inhibitor SU5402 indicated that FGF-2 accounted for the protective activity. We propose FGF-2 negative feedback as potentially important in microvascular remodelling.