ON THE POSTJUNCTIONAL α‐ADRENORECEPTORS IN RAT CEREBRAL AND MESENTERIC ARTERIES

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Abstract
The contractile response to exogenously applied noradrenaline (NA) [norepinephrine] was examined in vitro in tubal segments (0.2-0.1 mm in diameter) of rat middle cerebral (MCA), basilar (BA) and mesenteric (MA) arteries. In the MCA, the maximum contractile response to NA (10-4 M) was considerably smaller than that induced by K+ (124 mM) or 5-hydroxytryptamine (10-5 M), whereas the inverse relationship was found in the MA. NA usually failed to elicit contraction in the BA even in the presence of propranolol and cocaine. In the MCA, propranolol (3 .times. 10-7 M) enhanced the maximum contractile response to NA by .apprx. 100% without affecting the potency of the agonist. In the MA, propranolol had no effect on the concentration-response relationship for NA. Cocaine (10-5 M) or 6-hydroxydopamine pretreatment increased the NA sensitivity of the MA by a factor of 3, whereas these procedures failed to influence the NA sensitivity of the MCA. A marked stereoselectivity was found in the MCA, as (-)-NA was > 100 times more potent than (+)-NA as a contractile agent. The order of potency of a series of .alpha.-adrenoreceptor agonists was (-)-adrenaline > oxymetazoline > (.+-.)-NA .apprxeq. (-)-phenylephrine > methoxamine in the MCA and (.+-.)-NA > (-)-phenylephrine in the MA. Clonidine failed to elicit contraction in concentrations lower than 3 .times. 10-4 M in both types of artery. Prazosin was from 3-4 orders of magnitude more potent than rauwolscine in inhibiting NA-induced contractions in the MCA and MA. The pA2 values for, respectively, prazosin and rauwolscine were 9.3 and 5.4 in the MCA and 9.7 and 6.8 in the MA. The slope of the Schild plot deviated significantly from unity only for rauwolscine in the MA (0.64). The contractile response to exogenous NA in the MCA and MA is mediated mainly by stimulation of .alpha.1-adrenoreceptors, although a small contribution of postjunctional .alpha.2-adrenoreceptors in the MA cannot be excluded. In contrast to the MCA, the BA appears to lack contraction-mediating .alpha.-adrenoreceptors, indicating regional differences in the .alpha.-adrenoreceptor distribution in the rat cerebrovascular bed.

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