Influences of the endothelium and hypoxia on α1‐ and α2‐adrenoceptor‐mediated responses in the rabbit isolated pulmonary artery

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Abstract
The effects of the inhibitor of nitric oxide synthase, Nω‐nitro‐l‐arginine methylester (l‐NAME, 10−4 m), mechanical disruption of the endothelium and hypoxia on contraction to noradrenaline (α1‐ and α2‐adrenoceptor agonist), phenylephrine (α1‐adrenoceptor agonist) and UK 14304 (α2‐adrenoceptor agonist) were compared in the rabbit isolated pulmonary artery. The effects of the selective antagonists rauwolscine (10−6 m, α2‐adrenoceptors) and prazosin (10−7 m, α1‐adrenoceptors) on the contractions to noradrenaline before and after exposure to l‐NAME were also assessed. Noradrenaline, phenylephrine and UK 14304 all produced concentration‐dependent increases in vascular tone. The responses to noradrenaline were sensitive to both rauwolscine and prazosin (effect of prazosin >> rauwolscine). l‐NAME increased the potency of both noradrenaline and UK 14304, and also the maximum tension achieved. It had no effect on the responses to phenylephrine. After l‐NAME, contractions to noradrenaline, although still sensitivie to both rauwolscine and prazosin, were now more sensitive to inhibition by rauwolscine. Endothelium removal augmented the potency and maximum contractions to noradrenaline, phenylephrine and UK 14304. Hypoxia decreased both the potency of phenylephrine and its maximum contractile response, but increased the maximum response to noradrenaline without effecting responses to UK 14304. In conclusion, in the rabbit pulmonary artery, augmentation of contractile responses to noradrenaline by l‐NAME involves a potentiation of α2‐adrenoceptor‐mediated contraction probably through an effect on the synthesis of endothelium‐derived nitric oxide. Experimental hypoxia had differential effects on all three agonists and did not mimic the effect of nitric oxide synthase inhibition.