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Hypertension, Vol 24, 189-194, Copyright © 1994 by American Heart Association

ARTICLES

Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation

K Ando and T Fujita
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.

We designed the present study to clarify whether the intracellular pH change by ammonium chloride influences endothelium-dependent relaxation in thoracic aorta of 9-week-old Sprague-Dawley rats. Intracellular alkalinization with 3 mmol/L ammonium chloride, which did not affect resting vascular tone, attenuated acetylcholine-induced relaxation but not nitroglycerin vasodilation. Acetylcholine relaxation was more inhibited by a shorter duration of treatment. Thus, change in intracellular pH may be important in the effect because the alkalinizing effect of ammonium chloride disappears gradually. In support of this, the proton ionophore nigericin abolished the effect. Also, amiloride shortened the effect of ammonium chloride, suggesting that intracellular pH plays a role: sodium-proton antiport antagonizes the disappearance of ammonium chloride-induced intracellular alkalinization. The synthesis of vasoconstrictor prostaglandins, such as thromboxane A2, may be stimulated during acetylcholine treatment, resulting in the attenuation of acetylcholine relaxation, because the relaxation was abolished by treatment with the phospholipase A2 inhibitor quinacrine, cyclooxygenase inhibitor indomethacin, prostaglandin H2/thromboxane A2 receptor antagonist S1452, and thromboxane A2 synthase inhibitor dazmegrel. Phospholipase A2 may contribute to the effect of intracellular alkalinization, which is compatible with the fact that the optimal pH of phospholipase A2 is neutral to alkaline. In addition, superoxide dismutase attenuated the effect of ammonium chloride. In conclusion, intracellular alkalinization by ammonium chloride attenuated acetylcholine-induced relaxation, possibly through the interrelated production of both thromboxane A2 and superoxide radicals.

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