Possible prostacyclin involvement on disparate tonic responses to “in vitro” norepinephrine in circular and in longitudinal preparations from rat thoracic aorta

Abstract

In view of existing reports documenting that “in vitro” norepinephrine (NE) contracts ring-shaped rat aortic preparations, whereas it relaxes arterial strips mounted in longitudinal fashion within an organ bath: it was decided to explore possible reasons which may account for such disparate: actions of the same ogonist on the same tissue. Isolated rings (circular preparations) obtained from rat thoracic aortae responded to increasing concentrations of NE with dose-dependent tonic enhancement, not significantly affected by the presence of indomethacin (10⁻⁶M); whereas, preincubation with phentolamine (10⁻⁶M), yohimbine (10⁻⁷M)or prazosin (10⁻⁸M), shifted significantly to the right points of the positive inotropic dose-response curve for NE. On the contrary longitudinally mounted preparations of rat aortic stips, reacted to increasing concentrations of NE with dose-dependent relaxation, an effect not modified by the presence of a beta-adrenoreceptor blocker, namely propranolol (10⁻⁶M). However, in presence of alpha-adrenoreceptor blockers, such as phentolamine (10⁻⁶M), yohimbine (10⁻⁷M) or prazosin (10⁻⁸M), the negative inotropic dose-response curve for NE was shifted to the right whereas in the pres nce of indomethacin (10⁻⁶M) or of tranylcypromine (2.5×10⁻⁴M), the NE-induced relaxation was either abolished or significantly displaced to the right, respectively. In another series of experiments the generation of labelled 6-keto-prostaglandin F₁ α(the most important non-enzymatic metabolite of prostacyclin) by chopped rat aortae incubated for one hour with (1-¹⁴C)-arachidonic acid, was explored and found to be significantly enhanced by the delivery of NE (3 × 1O⁻⁶M). The present evidence suggests that NE acting on alpha-adrenoreceptors, induces in longitudinal and in chopped arterial preparations, but not in aortic rings, an inhibitory relaxing factor, presumably produced by the endothelium. This factor is probably prostacyclifor the relaxing effects of the agonist were negatively influence by indomethacin and by tranycypromine, two known antagonists of PGI₂ formation. In vascular rings (circular arterial preparations) the tonic stimulatory action of NE (not affected by preincubation with indomethacin) was the only evident inotropic effect of the agonist presumably because the extensive handling of the tissue as well as the anchoring procedure followed to mount arterial preparations within the bath for contractile recordings, may produce de-endothelization. Moreover, the notion is advanced that the apparently greater aortic prostacyclin synthesis after NE in preparations with better preserved integrity may represent a local modulating mechanism, controlling vascular responses to sympathetic activation.