MODULATION OF L-TYPE CA²⁺ CHANNELS IN RAT AORTIC SMOOTH MUSCLE BY N-3 POLYPHENOL

Alikhon Khasanov*, Sirojiddin Omonturdiev, Shokhida Kadirova, Muxtorjon Mamajanov, Qahramon Niyozov, Ulugbek Gayibov, Rakhmatilla Rakhimov

The present study investigated the vasorelaxant activity and underlying mechanisms of N-3 polyphenol on isolated rat aortic rings. Smooth muscle contraction is largely dependent on intracellular Ca²⁺ concentration, regulated through multiple pathways including voltage-dependent Ca²⁺ channels (VDCCs). Depolarization with 50 mM KCl induced a sustained contraction mediated mainly by activation of L-type Ca²⁺ channels. N-3 polyphenol (10–50 µM) significantly inhibited KCl-induced contraction in a dose-dependent manner, producing maximal relaxation of 79.3 ± 2.6% at 50 µM with an IC₅₀ value of 34 µM. In Ca²⁺-free Krebs solution, cumulative addition of CaCl₂ elicited concentration-dependent contraction, which was markedly attenuated by pre-incubation with N-3 polyphenol (50 µM), indicating blockade of extracellular Ca²⁺ influx. Furthermore, pretreatment with verapamil (0.1 µM), a selective L-type Ca²⁺ channel blocker, reduced contraction by 50 ± 2.5%, and the subsequent addition of N-3 polyphenol (34 µM) further decreased tension by 18.3 ± 2.7%. These findings demonstrate that the vasorelaxant effect of N-3 polyphenol is mediated primarily through functional inhibition of L-type Ca²⁺ channels, suggesting its potential as a membrane-targeting vasodilator with possible antihypertensive properties.