Insulin-Dependent Relaxation Modulation by Calcium-Activated Potassium Channels in Uterine Artery from Pregnant and Non-Pregnant Rats

Insulin-Dependent Relaxation Modulation by Calcium-Activated Potassium Channels in Uterine Artery from Pregnant and Non-Pregnant Rats

• Autor
• Rinaldo Rodrigues dos Passos Junior
• Co-autores
• Vanessa Dela Justina , Fernanda Privieiro , Clinton Webb , Fernanda Regina Giachini
• Resumo

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  Introduction: Insulin plays important hemodynamic effects on endothelial cells during pregnancy promoting vasodilation. Calcium-Activated Potassium (KCa) channels activity increases during pregnancy and its inhibition reduces uterine blood flow. We aimed to investigate whether KCa channels mediate insulin-dependent relaxation in the uterine artery during the pregnant (P) and non-pregnant (NP) state. Methods: Female Sprague-Dawley rats (220-270g) were separated into P and NP (n=7/group). On the 21st day of gestation rats were killed, and the uterus was removed. Approval by Animal Care and Use Committee of Augusta University (#2009-0226). Concentration-response curves (CRC) to insulin and acetylcholine were performed to evaluate the uterine artery relaxation; and western blotting was performed to quantify the KCa channels types (SK, BK, and IK) expression. Statistical analysis was performed by Student’s T-test or ANOVA followed by Tukey’s post-test. Results: P rats displayed decreased vascular content of BK compared do NP (p=0,0461). CRC to insulin was greater in NP than P (%, 80±8 vs. 51±6). KCa channels inhibition attenuated insulin-induced maximum relaxation in NP (~33%) which was abolished by L-NAME only to clotrimazole (IK inhibitor) and apamin (SK inhibitor). Regarding P animals, CRC to insulin was decreased in the presence of iberiotoxin [BK inhibitor; (~30%)]. Incubation with L-NAME abrogated the relaxation. Endothelium-dependent relaxation to acetylcholine was increased in P compared to NP (pD2, 6.6±0.06 vs. 6.9±0.07). Incubation with iberiotoxin reduced maximal response in NP compared to vehicle (Emax, 70±4 vs. 93.8±2), whereas P rats displayed decreased vasodilation to clotrimazole (Emax, 79.5±3) and iberiotoxin compared to vehicle (Emax, 59±4 vs. 99±2). Conclusion: KCa channels partially modulate insulin-dependent relaxation in the uterine artery from NP rats, but in P rats, this response is decreased, probably due to reduced insulin sensitivity. Furthermore, in P animals, the insulin-dependent relaxation is mediated by NO whereas in NP rats, other mediators are also involved.

   

• Palavras-chave
• insulin; relaxation; KCa channels.
• Modalidade
• Pôster
• Área Temática
• Sinalização celular