Subendothelial beta 2-adrenoceptors in the rat vena cava: facilitation of noradrenaline release via local stimulation of angiotensin II synthesis

Abstract

Preparations of the cranial segment of the rat inferior vena cava preincubated with 3H-noradrenaline were superfused in the presence of desipramine and corticosterone. Tritium overflow was stimulated electrically (2 Hz). The experiments were carried out in spirally cut strips with or without intima or in segments ligated at both ends and superfused either on the adventitial side ("conventionally") or "inside out". In spirally cut strips electrically evoked 3H overflow was increased by isoprenaline and procaterol, but much less so by prenalterol. Adrenaline 1 nmol/l increased overflow, but at high concentrations it reduced it, just as noradrenaline did at all concentrations. The concentration-response curve for isoprenaline was shifted to the right by propranolol (apparent pA2:8.29) and even more so by ICI 118-551, whereas atenolol was less potent (apparent pA2:6.42). Rauwolscine which, given alone, increased the evoked 3H overflow antagonized the inhibitory effect of noradrenaline (apparent pA2:7.58). These findings indicate that beta 2- and alpha 2-adrenoceptors mediating facilitation and inhibition of noradrenaline release, respectively, are present in the vena cava. The response to isoprenaline (at all concentrations) was considerably lower in segments superfused "conventionally" than in spirally cut strips, but no difference was observed with respect to the effects of noradrenaline, rauwolscine and angiotensin II. The effect of isoprenaline was clearly more pronounced in segments superfused "inside out" than in segments superfused "conventionally". In spirally cut strips angiotensin II increased 3H overflow. This effect was antagonized by saralasin, suggesting the involvement of facilitatory angiotensin receptors. In spirally cut strips or segments superfused "inside out", saralasin or captopril considerably attenuated the facilitatory effect of isoprenaline on 3H overflow. Conversely, in the presence of isoprenaline, captopril inhibited the electrically evoked 3H overflow in spirally cut strips, whereas in the absence of isoprenaline, captopril was ineffective. In conclusion, angiotensin receptors and alpha 2-adrenoceptors appear to be located on the sympathetic nerve endings, but a major part of the beta 2-adrenoceptors probably is subendothelial (most likely on smooth muscle cells). Angiotensin II, synthesized in response to beta 2-adrenoceptor activation, probably stimulates angiotensin receptors on the noradrenergic nerves, leading to an increase in noradrenaline release.