Angiogenic growth factors are new and essential players in the sustained relaxin vasodilatory pathway in rodents and humans
| Autor: | Jacqueline Novak, J. Peter Rubin, Kirk P. Conrad, Leslie A. Danielson, Jonathan T. McGuane, Julianna E. Debrah |
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| Rok vydání: | 2011 |
| Předmět: |
Placental growth factor
medicine.medical_specialty Indoles medicine.medical_treatment Vasodilation Angiogenesis Inhibitors Biology In Vitro Techniques Matrix Metalloproteinase Inhibitors Peptides Cyclic Article chemistry.chemical_compound Mice Pregnancy Internal medicine Internal Medicine medicine Animals Humans Pyrroles Rats Long-Evans Receptor Relaxin Renal circulation omega-N-Methylarginine urogenital system Growth factor Arteries Dipeptides Receptor Endothelin B Recombinant Proteins Endothelin B Receptor Antagonists Rats Vascular endothelial growth factor Mice Inbred C57BL Endocrinology medicine.anatomical_structure Receptors Vascular Endothelial Growth Factor chemistry Omega-N-Methylarginine Matrix Metalloproteinase 2 Female Nitric Oxide Synthase hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 57(6) |
| ISSN: | 1524-4563 |
| Popis: | Relaxin is emerging as an important vasodilator of pregnancy and is being tested for afterload reduction in acute heart failure. However, the mechanisms underlying relaxin-induced vasodilation are incompletely understood. The aims of this study were to establish a new in vitro model for relaxin-induced vasodilation and to use this approach, as well as chronically instrumented, conscious rats, to investigate the role of angiogenic growth factors in the relaxin vasodilatory pathway. Incubation of rat and mouse small renal arteries with recombinant human H2 relaxin for 3 hours in vitro attenuated myogenic constriction, which was blocked by inhibitors of gelatinases, the endothelin B receptor, and NO synthase. These findings corroborate ex vivo observations in arteries isolated from relaxin-infused nonpregnant and midterm pregnant rats, thereby validating the new experimental approach and enabling the study of human arteries. Incubation of small human subcutaneous arteries with relaxin for 3 hours in vitro also attenuated myogenic constriction through the same molecular intermediates. Vascular endothelial growth factor receptor inhibitor SU5416, 3 different vascular endothelial growth factor, and 2 different placental growth factor neutralizing antibodies prevented relaxin from attenuating myogenic constriction in rat and mouse small renal and human subcutaneous arteries. SU5416 administration also prevented relaxin-induced renal vasodilation and hyperfiltration in chronically instrumented, conscious rats. Small renal arteries isolated from these rats demonstrated increased matrix metalloproteinase 2 activity in the relaxin-infused group, which was not prevented by SU5416. We conclude that there is concordance of relaxin vasodilatory mechanisms in rats, mice, and humans, and angiogenic growth factors are novel and essential intermediates. |
| Databáze: | OpenAIRE |
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