Sympathetic innervation and α‐adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint

Abstract

1 Experiments were performed to determine the nature of adrenoceptors mediating neurally-induced vasoconstriction of blood vessels in the posterior region of the rabbit knee joint capsule. 2 Electrical stimulation of the posterior articular nerve resulted in frequency-dependent vasoconstriction which was maximal at 10 Hz. This response was mediated predominantly by a2-adrenoceptors as it was only slightly reduced by prazosin administration and was not only abolished but converted into a dilator response by the a2-adrenoceptor antagonist rauwolscine. Further experiments with another specific al-adrenoceptor antagonist YM-12617 showed that the frequency-response curve in the presence of this antagonist did not differ significantly from control. 3 Neurally-induced vasoconstriction did not appear to have a purinergic component as it was unaffected by the P2x-purinoceptor desensitiser a, methylene ATP. 4 The rank-order of potency of a-adrenoceptor agonists given as a bolus by close intra-arterial injection was: adrenaline = UK-14304 > clonidine> phenylephrine, suggesting that the vasoconstrictor effects were mediated predominantly by postjunctional a2-adrenoceptors. 5 The M2-adrenoceptor antagonist rauwolscine converted the constrictor response to close intra-arterial injection of adrenaline into a dilator response. The vasoconstrictor responses to UK-14304, clonidine and phenylephrine were substantially inhibited by rauwolscine. The a,-adrenoceptor antagonist prazosin failed to inhibit the vasoconstrictor responses to adrenaline, clonidine and UK-14304 and resulted in enhancement of their constrictor effects. 6 The enhancement of the responses to the a, and a2 agonists by prazosin appeared to be specifically related to this agent as administration of YM-12617 did not show such enhancement. The dose-response curves to both clonidine and UK-14304 in the presence of YM-12617 did not differ significantly from control responses. Responses to phenylephrine were significantly reduced by YM-12617, indicating the presence of post-junctional a,-adrenoceptors. 7 These results show almost complete reversal of the adrenoceptor profile compared to results obtained in an earlier in vitro study, where responses were mediated predominantly by ax,-adrenoceptors with a small population of postjunctional a2-adrenoceptors (Ferrell & Khoshbaten, 1989). This suggests that the differing environment in vitro may not completely reflect the conditions prevailing in vivo.

Alteration in α- and β- adrenoceptor profile of rabbit-knee-joint blood vessels due to chronic inflammation

“…Compared to previous studies in normal joint blood vessels in which β 1 -adrenoceptors predominated [20] and equal β 1 and β 2 responses in acutely inflamed joints [23], the predominant β 2 response found in the present study shows that the shift of β 1 -to β 2 -adrenoceptor response which began by the process of acute inflammation was continued in the course of chronic inflammation. The functional significance of this alteration is not evident at present and needs to be investigated.…”

“…Alteration in β-adrenoceptor profile Regarding the joint blood vessels response to β-adrenoceptor agonists, the maximum increase in blood flow to 25 nmol of the nonselective β-adrenoceptor agonist isoprenaline in the present study was 8% compared to about 26% in acutely inflamed [23] and 36% in normal [20] joints found in our previous studies. A same pattern of decrease is found in response to selective β 1 -and β 2 -agonists dobutamine and salbutamol, respectively, with the process of inflammation.…”

“…Arterial blood pressure was continuously monitored via a cannula inserted into the left carotid artery and connected to a pressure transducer (Beckman Physiograph model R611, USA). With the above anesthetic regime, the blood pressure was found to be stable during the course of the experiment [19,20].…”

“…A minimum of 30 min was allowed to lapse before subsequent PAN stimulation or adrenoceptor agonist administration. Previous studies have shown that these doses and duration are sufficient to block the relevant adrenoceptors, and also for blood pressure to stabilize at a new level [19,20,23]. Only one α-antagonist of nonselective α-adrenoceptor agonist adrenaline (Ad) and selective α 1 -and α 2 -adrenoceptor agonists phenylephrine (Pe) and clonidine (Cl), in control conditions (a), and 45 min after intravenous administration of nonselective α-adrenoceptor antagonist phentolamine (b), in one of the animals of series 1.…”

“…Also, nitric oxide (NO) production did not appear to be changed by the process of acute inflammation in the joint [18]. In relation to the question of whether a change in adrenoceptor profile of articular blood vessels was responsible for the reduction in sympathetic vasoconstriction tone, a shift from α 2 -toward α 1 -and from β 1 -toward β 2 -adrenoceptor response was shown to occur in acutely inflamed joint [23], while studies in the normal joint had shown a predominance of α 2 -and β 1 -postjunctional adrenoceptor subtypes mediating neurally sympathetic effects on joint blood vessels [19,20]. Badavi et al [1] showed a reduction in response to selective α 1 -adrenoceptor agonist phenylephrine, in chronically inflamed rat knee joint blood vessels.…”