Role Of Anion Channel In Maintaining Vascular Tone In Rat Aorta

Vascular tone plays a key role in the maintenance of blood pressure. Anion channels are extensively expressed in the cardiovascular system, but their roles in the modulation of vascular tone are poorly understood. We, therefore, investigated the role of anion channels on the vascular tone. Norepinephrine (NE)-evoked contraction was observed in rat aorta by using routine blood vascular perfusion in vitro. The experimental designs were as follows:1. Vasorelaxing effects of anion channel blocker were observed.2. The change of vascular tone was observed after different ion substitution.3. Role of volume-regulated Cl channels(VRCC, Ic1.vol) on vascular tone was observed.4. Effects of anion channel blocker on contraction induced by KC1 (60 mmol/L) were observed.5. Effects of anion channels on the influx of extracellular calcium and the release of intracellular calcium were observed. The major results were summarized below:1. The anion channel blockers niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) produced inhibitory effects on NE-evocked contraction in the aorta.2. NE-evoked contraction was not significantly changed after the extracellular Na+ was replaced by choline and C4H12N+, but was relaxed when the extracellular Cl- was replaced by glutamate and gluconate. Moreover, the vasoconstriction induced by NE was further enhanced with the replacement of the extracellular Cl" by Br" and SCN", which was still sensitive to either NFA or NPPB.3. NE-evoked contraction was decreased in hypertonic solution, and vasorelaxing effect of anion channel blocker was attenuated compared with those in normal Tyrode solution. However, the constriction induced by NE was further enhanced when exposure of the aorta to hypotonic solution, which was inhibited by either NFA or NPPB.4. Contraction induced by 60 mmol/L KC1 was completely inhibited by NFA and NPPB.5. After pretreated with nifedipine to block the influx of extracellular calcium, the vessels did not contract when they were stimulated by 60 mmol/L KC1 solution; On the other hand, after pretreated with thapsigargin to deplete the intracellular calcium stores, the vessel remained the ability to contract when stimulated by 60mmol/L KCl solution. The anion channel blockers NFA and NPPB abolished the KCl-induced contraction of vessels which were pretreated by thapsigargin.6. The anion channel blockers NFA and NPPB inhibited the NE -induced contraction of vessels in Ca2+-free solution.These results suggest: 1) Anion channels play an important role in the regulation of blood vascular tone; 2) NE-stimulated contraction is not influenced by extracellular sodium; 3) Vascular tone can be affected by anion channel's activity; 4) The activation of anion channels do not depend on release of intracellular calcium; 5) Anion channels may be involved in the regulation of vascular tone through modulating the influx of extracellular calcium and the release of intracellular calcium.In conclusion, anion channels play an important role in the regulation of blood vascular tone. Anion channels affect vascular tone through modulating the influx of extracellular calcium and the release of intracellular calcium, which provide new insight into the understanding of salt-sensitivity hypertension.