Alteration in α‐ and β‐Adrenoceptor Profile of Rabbit Knee Joint Blood Vessels due to Acute Inflammation

Abstract

Experiments were performed to investigate the nature of α‐ and β‐adrenoceptors in blood vessels supplying the posterior capsule of the acutely inflamed rabbit knee joint, and results were compared to findings from previous experiments on the normal joint, to assess any alteration which may occur in the adrenoceptor profile due to the inflammation process. Electrical stimulation of the posterior articular nerve resulted in vasoconstriction which was reversed to vasodilatation by phentolamine and yohimbine. The dose‐response curves to close intra‐arterial injection of α‐adrenoceptor agonists showed a rank‐order potency of: adrenaline = phenylephrine = clonidine. The adrenaline dose‐response curve was shifted to the right by administration of antagonists with a rank‐order potency of: phentolamine = yohimbine = prazosin. At this stage of the experiments there was an equal response of α1‐ and α2‐adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. In another group of animals the neurally mediated vasodilatation, which appeared after administration of phentolamine, was completely blocked by propranolol, and was reduced by about 50% by atenolol. The dose‐response curves to close intra‐arterial injection of β‐adrenoceptor agonists showed a rank‐order potency of: isoprenaline > salbutamol = dobutamine. The isoprenaline dose‐response curve was shifted to the right by administration of antagonists with a rank‐order potency of: propranolol > atenolol. These experiments also showed an almost equal response of β1‐ and β2‐adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. Overall, compared to previous experiments on the normal joint in which α2‐ and β1‐adrenoceptor responses predominated, acute inflammation resulted in a shift from α2‐ towards α1‐ and from β1‐ towards β2‐adrenoceptor responses.

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

“…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.…”

“…In normal joint blood vessels of the rabbit, a predominant α 2 -adrenoceptor response was shown. This was shifted toward α 1 -adrenoceptor response, due to the process of acute inflammation, until a balance between the two responses was reached [23]. In the present study, equal potency of selective α 1 -and α 2 -adrenoceptor antagonists prazosin and yohimbine, respectively, in blocking the vasoconstriction response to nerve stimulation revealed a balance between the two α 1 and α 2 responses in chronic inflammation state (Fig.…”

“…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.…”

“…The stimulus parameters were: width 1 ms, voltage 10 V, frequency 30 Hz, and duration 30 s, as shown that these stimulus parameters give rise to maximal vasoconstrictor response in normal and inflamed joints [22,23]. A 0.9-mm diameter fiber-optic probe connected to a laser Doppler flow meter (DRT4: Moor Instruments, Axminster, UK) provided a measure of relative changes in blood flow in the volume of tissue beneath the tip of the probe.…”

“…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.…”