Cardiac Post-Junctional Alpha₁- and Beta-Adrenoceptors: Effects of Chronic Chemical Sympathectomy with 6-Hydroxydopamine

Abstract

Alpha 1- and beta-adrenoceptor responsiveness and binding have been examined in cardiac tissues removed from guinea-pigs pretreated with 6-hydroxydopamine (6-OHDA) for 3 weeks. Results were compared with control tissues from sham-injected animals. Chemical sympathectomy with 6-OHDA resulted in an increase in the sensitivity of postjunctional beta-adrenoceptor-mediated responses to isoprenaline. No such increase was observed for the alpha 1-adrenoceptor-mediated responses to methoxamine. The increase in beta-adrenergic responsiveness was accompanied by a significant (P less than 0.05) 52% increase in the number of [3H]-dihydroalprenolol binding sites with no change in binding affinity. [3H]-Prazosin binding was not affected by pretreatment with 6-OHDA. The results suggest that cardiac beta- but not alpha 1-adrenergic responsiveness is regulated by the sympathetic innervation.

Differential regulation of adrenergic receptor development by sympathetic innervation

“…Thus, the removal of catecholamines precedes a decrease in adrenergic receptor levels and a corresponding decrease in agonist-induced phospholipase C activity. This contrasts with previous studies that indicate that removal of catecholamines by chemical or surgical sympathectomy results in increased receptor expression and agonist supersensitivity in both developing and adult animals (Yamada et al, 1980;Tenner et al, 1982;Chess-Williams et al, 1987. In addition, in vitro studies indicate that the presence of agonist results in downregulation of receptors and desensitization of responsiveness, whereas the removal of agonist results in upregulation of receptors and supersensitivity (Raymond et al, 1990;Collins et al, 1991Collins et al, , 1992 Although expression of adrenergic receptors in sweat glands does not follow the pattern one would expect based on in vitro studies of receptor regulation, the observation that decreased receptor levels coincide with changes in the sympathetic innervation suggests that the innervation influences receptor expression.…”

Noradrenaline desensitizes β‐ but not α‐adrenoceptor mediated cardiac responses in vitro

“…The lack of a desensitizing effect of noradrenaline at cardiac a-adrenoceptors lends support to the idea that this amine does not stimulate rat cardiac a,-adrenoceptors. Although some evidence exists to the contrary in the cat (Kaumann, 1970), several investigators have concluded that all the inotropic effects of noradrenaline on the heart are mediated solely via /3-adrenoceptors and only synthetic a-adrenoceptor agonists such as phenylephrine and methoxamine activate this receptor (Wagner, Schumann, Knorr & Reidemeister, 1980;Schumann, 1983;Williamson & Broadley, 1989;Chess-Williams, Austin & O'Brien, 1991). This lack of any observable effects of noradrenaline on myocardial a-adrenoceptors, however, may be due to an inhibitory effect of simultaneous Padrenoceptor stimulation, which has been shown to inhibit the inotropic effects mediated via myocardial a-adrenoceptors (Skomedal, Schiander & Osnes, 1988).…”

“…These results suggest that a-adrenoceptors are regulated by the degree of receptor activation as described for /3-adrenoceptors. In the heart, interruption of normal sympathetic transmission by chronic treatment with reserpine or 6-hydroxydopamine pro-duces a supersensitivity of cardiac P-adrenoceptor-mediated responses, whereas myocardial a-adrenoceptor responsiveness remains normal (Chess-Williams, Broadley & Sheridan, 1 987; Chess-Williams, Grassby, Broadley & Sheridan, 1987). In addition, a desensitization of myocardial Pbut not a-adrenoceptor-mediated responses has recently been reported to occur in human heart failure (Bohm, Diet, Feiler, Kemkas & Erdmann, 1988).…”