Amiloride acts as an alpha-adrenergic antagonist in the isolated rat tail artery

In the final concentration of 100 microM, amiloride increased substantially the overflow of endogenous noradrenaline and decreased that of 3,4-dihydroxyphenylethylene glycol from the rat tail artery into Krebs solution supplemented with 10 microM veratridine. The overflow of the amine into a 120 mM-K version of Krebs solution was unaffected by amiloride, while that of the glycol was reduced. Abolition of the contractile response to 10 microM veratridine by 2 microM phentolamine indicated that the response was due to release of endogenous noradrenaline. Addition of amiloride in the final concentrations of 10 and 100 microM caused relaxation of strips contracted by the alkaloid. The dose-response relations for exogenous noradrenaline measured in the absence or presence of 50 microM amiloride indicated that the drug acted as a reversible competitive alpha-adrenergic antagonist. The phentolamine-resistant component of the contractile response to the 120 mM-K solution was unaffected by 100 microM amiloride. Although the exact site of action of amiloride remains to be determined, it can be concluded that amiloride inhibits adrenergic transmission at a postsynaptic site at a step preceding elevation of myoplasmic Ca2+.