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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Gender differences in vascular reactivity to endothelin-1 (1-31) in mesenteric arteries from diabetic mice
Takayuki Matsumoto1, Mika Kakami, Tsuneo Kobayashi
1Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Insights
Endothelin-1 (1-31) significantly enhances vasoconstriction in female mice with chronic diabetes. This effect, mediated by Rho kinase and MAPK pathways, is not observed in male diabetic mice.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- Endothelin-1 (1-31) [ET-1 (1-31)] is a novel peptide with known biological effects.
- The impact of diabetes on ET-1 (1-31) vascular activity and potential gender differences remain unclear.
Purpose of the Study:
- To investigate potential gender differences in the vascular effects of ET-1 (1-31) in early and chronic diabetes.
- To explore the signaling pathways involved in ET-1 (1-31)-induced vasoconstriction in diabetic mesenteric arteries.
Main Methods:
- Mesenteric artery rings from control and streptozotocin (STZ)-induced diabetic mice (early and chronic phases) were exposed to ET-1 (1-31).
- Vascular contractions were measured.
- The effects of Rho kinase (Y27632), ERK1/2 (PD98059), and JNK (SP600125) inhibitors were assessed.
Main Results:
- In early diabetes, ET-1 (1-31)-induced contraction was similar in control and diabetic mice of both sexes.
- In chronic diabetes, ET-1 (1-31)-induced contraction was enhanced in female diabetic mice but not in male diabetic mice.
- The enhancement in female diabetic mice was attenuated by Y27632, PD98059, and SP600125.
Conclusions:
- Established diabetes specifically enhances ET-1 (1-31)-induced vasoconstriction in female mice.
- This enhancement is linked to increased activity in Rho/Rho kinase and MAPK signaling pathways.
- Findings highlight potential sex-specific vascular dysregulation in diabetes.
Abstract:
Endothelin-1 (1-31) [ET-1 (1-31)], a novel member of the ET family, comprises 31 amino acids and is derived from the selective hydrolysis of big ET-1 by chymase. Although ET-1 (1-31) reportedly exerts biological effects by direct or indirect [via its conversion to ET-1 (1-21)] mechanisms, it is unclear whether in diabetes the vascular effects of ET-1 (1-31) display gender differences. We investigated this question by exposing mesenteric artery rings to ET-1 (1-31), using arteries from mice in the early or chronic phase of diabetes. In the early stage of diabetes, the ET-1 (1-31)-induced contraction was similar between age- and sex-matched control and streptozotocin (STZ)-induced diabetic mice. In the chronic stage of diabetes, the ET-1 (1-31)-induced contraction was enhanced in diabetic female mice, but not in diabetic male mice (vs. both age-matched control and early-stage diabetic mice). This enhancement was largely prevented by Y27632 (Rho kinase inhibitor), PD98059 [inhibitor of extracellular signal related kinases 1 and 2 (ERK1/2)], or SP600125 [C-jun terminal kinase (JNK) inhibitor]. These data indicate that the ET-1 (1-31)-induced vasoconstriction in the mesenteric artery may be specifically enhanced in established diabetic female mice, and that this enhancement may be due to alterations in the activities of Rho/Rho kinase or mitogen-activated protein kinase.
