Inhibitory Effects of Clonidine on Responses to Sympathetic Nerve Stimulation in the Pithed Rat

Abstract

I The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2 Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3 Clonidine produced a postsynaptic a-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4 The effects of clonidine, naphazoline and oxymetazoline on pre-and postsynaptic a-adrenoceptors were determined. 5 The presynaptic a-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic a-adrenoceptor agonist activity. 6 The presynaptic a-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7 The results support the view that presynaptic a-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic a-adrenoceptors of different sympathetic nerve endings.

Lack of Correlation Between Presynaptic Inhibition of Noradrenaline Release and End Organ Responses During Nerve Stimulation

“…In addition LD 3098 produced a smaller decrease of basal heart rate than that obtained with clonidine infusions. Furthermore clonidine, unlike LD 3098, reduced responses of the heart and nictitating membrane to sympathetic nerve stimulation, indicating stimulation of presynaptic inhibitory ax-adrenoceptors subserving a modulator role at sympathetic neuroeffector junctions (Drew, 1976;Doxey & Everitt, 1977;Steppeler et al, 1978). Attention should be drawn to the fact that the nictitating membrane contracts after clonidine and consequently baseline increases could mask the effects of nerve stimulation.…”

“…However, in many studies, especially those in vivo, the assessment of the affinity of drugs for presynaptic 0007-1188/80/050081 -10 $01.00 z-adrenoceptors has been indirect and based on measurement of changes in end organ response, especiatly heart rate (Armstrong & Boura, 1973;Drew, 1976;Doxey & Everitt, 1977;Roach et al, 1978; Constantine, Weeks & McShane, 1978). In some cases this has been done with little, if any, attention being paid to alterations in sensitivity of the end organ responses after drug treatment despite the early paper by Boissier, Giudicelli, Fichelle, Schmitt & Schmitt (1968) which demonstrates that clonidine modifies the blood pressure response to injected noradrenaline in anaesthetized dogs.…”

Reduced peripheral presynaptic adrenoceptor sensitivity following chronic antidepressant treatment in rats

“…Artificial respiration was instituted using a Harvard rodent respirator (2.2 ml per stroke, 50 strokes min-'), the jugular vein catheterized for intravenous injection of drugs, and blood pressure measured from a carotid artery, using a Statham P 23 Db pressure transducer and BrushGould recorder. Contractions of the left vas deferens in response to sympathetic stimulation were obtained as described by Doxey & Everitt (1977). Following equilibration of responses to supramaximal electrical stimulation (280 mA, 50 gs, 6 Hz for 3 s every 1 min), a single sub-maximal dose of clonidine (1 gg kg-) was injected intravenously and the degree of inhibition of contractile response determined.…”

α2c‐Adrenoceptor‐modulated release of noradrenaline in human right atrium

“…In fact, the first evidence for heterogeneity of the a2-adrenoceptor class was obtained when pre-1 Author for correspondence. synaptic a2-autoreceptors were compared in rat heart and vas deferens (Doxey & Everitt, 1977). In rabbit brain cortex, pulmonary artery, kidney and atria the a2-autoreceptors have been characterized as a2A (Limberger et al, 1991;1995a;Molderings & G6thert, 1992;Trendelenburg et al, 1993).…”