Mechanism of inhibition of rat caudal artery contraction by amiloride.


Amiloride (N-amidino-3,5-diamino-6-chloropyarzine carboxamide), a potassium sparing diuretic, decreases blood pressure and inhibits vascular smooth muscle contractility in rats. The purpose of these experiments was to investigate the mechanisms by which amiloride inhibits contraction of rat caudal artery. Caudal artery rings were mounted in a muscle chamber that was continuously flushed with circulated bathing medium and the contractions were recorded through a force transducer. The results demonstrate that amiloride competitively inhibited the norepinephrine-stimulated contraction of arterial rings (pA2 = 5.2). This suggests that amiloride and norepinephrine (NE) interact at the same site. The concentration required to produce half-maximum inhibition (IC50) of contraction produced by 10(-6) M norepinephrine was 48 +/- 6 microM. Amiloride (100 microM) shifted the concentration-response curves of norepinephrine and methoxamine to the right without significantly affecting the maximum contraction produced by these agonists. The EC50 value and the threshold concentration of both norepinephrine and methoxamine were increased by about 10-fold in the presence of 100 microM amiloride. Amiloride-induced inhibition of norepinephrine-stimulated contraction was reversible following removal of the drug. Amiloride-induced inhibition of vascular smooth muscle contraction was not blocked by ouabain or monensin. Amiloride at concentrations up to 100 microM did not inhibit K+ stimulated contractions. From these results we conclude that amiloride reversibly inhibits vascular smooth muscle contraction by competing with alpha-adrenoceptor agonists for binding to alpha 1-adrenoceptors.


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@article{Sharma1988MechanismOI, title={Mechanism of inhibition of rat caudal artery contraction by amiloride.}, author={Ram V. Sharma and Luziane M Bendhack and Ramesh C Bhalla}, journal={Journal of cardiovascular pharmacology}, year={1988}, volume={12 2}, pages={152-9} }