Regional variation in the alpha-adrenergic receptors in the canine resistance vessels

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Vasoconstrictor effects of non-selective and relatively selective alpha1- and alpha2-adrenergic agonists (noradrenaline, phenylephrine, methoxamine, clonidine, and alpha-methylnora drenaline) and the inhibition of their vasoconstrictor effects by prazosin or yohimbine were studied in vivo in the renal and femoral vascular beds of pentobarbital anesthetized, beta-adrenergic and ganglion-blocked dogs. Some animals were additionally pretreated with methylphenidate to block uptake of the agonists by the nerves. In the femoral vascular bed the following results were obtained: 1. Clonidine was equipotent with noradrenaline and about 15-fold more potant than phenylephrine in reducing the blood flow. 2. Yohimbi while prazosin had practically no effect on, the induced by clonidine. 3. Vasoconstriction induced by phenylephrine or methoxamine was antagonized by prazosin but not by yohimbine. The results obtained in the renal vascular bed were as follows: 1. Clonidine was about 12-fold weaker than noradrenaline and nearly equipotent with phenylephrine in reducing blood flow. 2. Both yohimbine and prazosin were weak antagonists of the vasoconstriction induced by clonidine and tended to be additive. 3. Prazosin effectively antagonized the effects of phenylephrine or methoxamine. Noradrenaline and alpha-methylnoradrenaline caused vasoconstriction in both beds and their effects were inhibited by both antagonists which tended to be additive in either vascular bed.

These results provide further evidence that the vasoconstrictor effects of noradrenaline and other alpha-adrenergic agonists are mediated by both subtypes of alpha-adrenergic receptors in the blood vessels of the dog. Higher potency of clonidine in the femoral bed and its selective inhibition by yohimbine indicate that alpha2 subtype of adrenergic receptors predominate in this bed. Similar considerations in the reverse suggest that alpha1-adrenergic receptors predominate in the renal vascular bed of the dog. Thus, these results show that there is regional variation in the distribution of the subtypes of alpha-adrenergic receptors in the resistance vessels of the dog.