Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by α-adrenoceptors in the isolated rabbit papillary muscle

Summary

Under the conditions of different stimulation frequencies the inotropic effects of the α-adrenoceptor stimulating agents, methoxamine, naphazoline and oxymetazoline were studied on the isolated rabbit papillary muscle.

• 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10⁻⁵ to 3×10⁻⁴ M caused a significant and dose-dependent positive inotropic effect. At 10⁻³ M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5–1–1.5 Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10⁻⁶ M), in contrast to that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10⁻⁵ M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect.

• 2. The positive inotropic effect of methoxamine (10⁻⁴ M) as well as of naphazoline (10⁻⁵ M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10⁻⁶ M). Methoxamine (10⁻⁴ M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD′₂-value was 7.76.

• 3. In the presence of methoxamine (10⁻⁴ M) the developed tension in the lower range (0.05–1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (>1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10⁻⁶ M).

• 4. Papaverine (2×10⁻⁵ M) did not affect the positive inotropic effect of methoxamine.

• 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via α-adrenoceptors in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.