Role of alpha-adrenoceptors in constrictor responses of rat, guinea-pig and rabbit small arteries to neural activation.

1. We have investigated the adrenoceptors mediating the force and electrical responses of rat mesenteric small arteries (i.d. 100-300 microns). Some mechanical experiments were also performed using guinea-pig and rabbit mesenteric small arteries. 2. Vessels were mounted on an isometric myograph and stimulated either with short (3 s) trains of electric field stimuli (ca. 0.2 ms pulse width) at 25 Hz (nerve stimulation) or with 10 microM-exogenous noradrenaline. 3. Nerve stimulation caused a force response equal to ca. 40% of the response to exogenous noradrenaline and, in the rat vessels, excitatory junction potentials (EJPs), which normally summated to give a depolarization of ca. 10 mV (although action potentials were sometimes seen). 4. Almost complete and reversible inhibition of the force responses of all vessels to both exogenous noradrenaline and to nerve stimulation was obtained using prazosin (0.1 microM) or phentolamine (1 microM). 5. Irreversible blockade of alpha 2-receptors enhanced the force response of all vessels to nerve stimulation by ca. 50%, but did not affect the force response of rat and guinea-pig vessels to exogenous noradrenaline. In the rabbit vessels this force response was abolished by alpha 2-blockade. 6. Following alpha 2-blockade, in the rat vessels the alpha-antagonists prazosin (0.1 microM), phentolamine (0.1 microM), phenoxybenzamine (0.01 microM) and benextramine (10 microM) all totally abolished the force response to exogenous noradrenaline, and inhibited the response to nerve stimulation by at least 80%. Similar effects of phentolamine were seen in the guinea-pig and, for the response to nerve stimulation, in the rabbit vessels. 7. In the rat vessels, alpha-adrenoceptor antagonists did not affect the EJPs, but did inhibit the small depolarization which resulted from several seconds of nerve stimulation. The ATP analogue alpha, beta-methylene-ATP (3 microM) abolished the EJPs, but only slightly reduced the force responses. 8. The results suggest that the force response to nerve stimulation of the rat mesenteric small arteries is mediated primarily through alpha-adrenoceptors, but also to a small degree through non-alpha-adrenoceptors, possibly ATP receptors.