| Abstract: | The influence of the vascular endothelium on agonist-induced contractions and relaxations has been measured using intact segments of rat aorta. Contiguous rubbed segments were used as controls. Angiotensin II, histamine, noradrenaline, U46619 and UK14304 contracted both rubbed and intact tissues. The threshold spasmogenic concentrations of these agonists were lower in rubbed tissues than in intact preparations. The sensitivity and responsiveness of tissues to angiotensin II, histamine, noradrenaline and UK14304 were greater in rubbed than in intact tissues. Acetylcholine and histamine relaxed the established spasms of intact tissues but not those of rubbed preparations, These relaxant effects of acetylcholine were abolished by pre-incubation with haemoglobin. In the presence of prazosin, noradrenaline or UK14304 relaxed established contractions in intact tissues. These effects were antagonized by idazoxan or by pre-incubation with haemoglobin. In intact preparations, idazoxan had no effect on the spasmogenic sensitivity and responsiveness to UK14304. Pre-incubation with haemoglobin augmented the spasmogenic actions of noradrenaline, U46619 or UK14304 in intact tissues, but had no effect on these responses in rubbed preparations. Tissue concentrations of cyclic GMP were greater in intact than in rubbed tissues. A concentration of acetylcholine (10 microM) evoking just maximal mechanical inhibition produced a significant increase in cyclic GMP concentration in intact preparations. However, no detectable changes in cyclic GMP concentration were produced by UK14304 (10 microM) or by acetylcholine (30 nM), concentrations which were equi-effective in inhibiting mechanical activity. In the presence of threshold spasmogenic concentrations of noradrenaline, the contractile effects of angiotensin II were augmented and became comparable to those observed in rubbed preparations. In the presence of greater concentrations of noradrenaline, angiotensin II always produced an additional contraction. It is concluded that the presence of the vascular endothelium limits the spasmogenic action of a variety of agonists. Although spasmogens like noradrenaline and UK14304 can stimulate the release of endothelium-derived relaxing factor (EDRF) via alpha 2-adrenoceptors, the inhibitory effects of EDRF largely result from the spontaneous release of this substance. |
