Enhanced contractility in pregnancy is associated with augmented TRPC3, L-type, and T-type voltage-dependent calcium channel function in rat uterine radial artery
| Autor: | T. Hilton Grayson, Marianne Tare, Leo R. Leader, Paul P. Bertrand, Shaun L. Sandow, Timothy V. Murphy, Sevvandi Senadheera |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Calcium Channels L-Type Nifedipine Physiology Muscle Smooth Vascular Constriction Rats Sprague-Dawley Contractility Calcium Channels T-Type Phenylephrine TRPC3 Pregnancy Physiology (medical) Internal medicine medicine.artery medicine Animals Vasoconstrictor Agents Radial artery TRPC Cation Channels Voltage-dependent calcium channel business.industry Myography Anatomy Calcium Channel Blockers medicine.disease Rats Uterine Artery Endocrinology Vasoconstriction Pyrazoles Female Endothelium Vascular medicine.symptom business Muscle Contraction |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 305:R917-R926 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.00225.2013 |
| Popis: | In pregnancy, α-adrenoceptor-mediated vasoconstriction is augmented in uterine radial arteries and is accompanied by underlying changes in smooth muscle (SM) Ca2+ activity. This study aims to determine the Ca2+ entry channels associated with altered vasoconstriction in pregnancy, with the hypothesis that augmented vasoconstriction involves transient receptor potential canonical type-3 (TRPC3) and L- and T-type voltage-dependent Ca2+ channels. Immunohistochemistry showed TRPC3, L-type Cav1.2 (as the α1C subunit), T-type Cav3.1 (α1G), and Cav3.2 (α1H) localization to the uterine radial artery SM. Fluorescence intensity of TRPC3, Cav1.2, and Cav3.2 was increased, and Cav3.1 decreased in radial artery SM from pregnant rats. Western blot analysis confirmed increased TRPC3 protein expression in the radial artery from pregnant rats. Pressure myography incorporating pharmacological intervention to examine the role of these channels in uterine radial arteries showed an attenuation of phenylephrine (PE)-induced constriction with Pyr3 {1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino]phenyl]-5-(trifluoromethyl)-1 H-pyrazole-4-carboxylic acid}-mediated TRPC3 inhibition or with nifedipine-mediated L-type channel block alone in vessels from pregnant rats; both effects of which were diminished in radial arteries from nonpregnant rats. Combined TRPC3 and L-type inhibition attenuated PE-induced constriction in radial arteries, and the residual vasoconstriction was reduced and abolished with T-type channel block with NNC 55-0396 in arteries from nonpregnant and pregnant rats, respectively. With SM Ca2+ stores depleted and in the presence of PE, nifedipine, and NNC 55-0396, blockade of TRPC3 reversed PE-induced constriction. These data suggest that TRPC3 channels act synergistically with L- and T-type channels to modulate radial artery vasoconstriction, with the mechanism being augmented in pregnancy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|