Effect of clonidine on cardiac acceleration in pithed rats

1 The effect of (R)-a-methylhistamine, a selective H3-histamine receptor agonist, was examined on the neurogenic hypertension and tachycardia that is induced by stimulation of areas in the medulla oblongata of guinea-pigs. Electrical medullary stimulation (32 Hz, 3-5 s trains, 0.5-1.0 ms square pulse, 25-400 juA) produced intensity-dependent increases in blood pressure and a more variable tachycardia.2 (R)-ac-methylhistamine inhibited the hypertension and tachycardia due to submaximal CNS stimulation. The inhibition of hypertension by (R)-x-methylhistamine was dose-dependent (1O-300 tg kg-', i.v.) and was not seen at high intensities of stimulation. 3 (R)-o-methylhistamine (300 ptg kg-', i.v.) did not attenuate the pressor response to adrenaline (1 and 3 fLg kg-', i.v.), indicating that the effect of (R)-x-methylhistamine was not mediated by a postjunctional action on smooth muscle. 4 The inhibition of CNS-induced hypertension by (R)-x-methylhistamine (300 yg kg-', i.v.) was blocked by the H3 antagonists, thioperamide (ID50 = 0.39 mg kg-', iv.), impromidine (ID50 = 0.22 mg kg-, i.v.) and burimamide (ID50 = 6 mg kg-', i.v.). The rank order potency of these antagonists is consistent with activity at the H3B receptor subtype. Chlorpheniramine (30 ptg kg-', i.v.) and cimetidine (3 mg kg-', i.v.) did not antagonize the inhibition of CNS-hypertension by (R)-a-methylhistamine. 5 These results suggest that (R)-a-methylhistamine inhibits sympathetic hypertensive responses in guinea-pigs by activation of prejunctional H3-receptors, possibly located on postganglionic nerve terminals. Furthermore, on the basis of the rank order potency to different H3-antagonists, it appears that the H3B-receptor subtype is involved with H3-receptor responses on vascular sympathetic nerves.

Section: Discussionmentioning

confidence: 87%

Inhibition of sympathetic hypertensive responses in the guinea‐pig by prejunctional histamine H₃‐receptors

Hey¹,

Prado²,

Egan³

et al. 1992

“…As a consequence, antagonists which preferentially act on prejunctional a-adrenoceptors should, under certain circumstances, be capable of increasing the effector organ response to adrenergic nerve stimulation when used at concentrations where the post-junctional a-adrenoceptors are not significantly antagonized or where the post-junctional adrenoceptors are of a different type, as in the heart (Drew, 1976;Docherty & McGrath, 1977;Doxey, 1977;Langer, Adler-Graschinsky & Giorgi, 1977).…”

Section: Introductionmentioning

confidence: 99%

The EFFECTS OF Α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF TRANSMURALLY STIMULATED PROSTATIC AND EPIDIDYMAL PORTIONS OF THE ISOLATED VAS DEFERENS OF THE RAT

Brown

McGrath

Summers

1979

1 The effects of a-adrenoceptor agonists and antagonists on contractile responses of transmurally stimulated prostatic and epididymal portions of the rat isolated vas deferens were examined. 2 Responses to single stimuli consisted of two phases, the first predominant in the prostatic and the second in the epididymal portion. The first phase was resistant to a-adrenoceptor antagonists but the second was reduced in a dose-related manner in the order of potency prazosin > azapetine > phentolamine > labetalol > yohimbine. 3 Both phases of the response to a single stimulus were reduced by clonidine but only the first could be reliably restored by yohimbine. 4 Trains of transmural stimuli produced biphasic. responses, an early rapid component predominant in the prostatic and a slower secondary component predominant in the epididymal portion. The effects of a-adrenoceptor antagonists on these responses were complex. Prazosin produced the most straightforward inhibition of responses with relative resistance of the early rapid component. Only yohimbine and phentolamine produced increases in responses which could be pre-junctional in origin. 5 The a-adrenoceptor agonists, oxymetazoline and clonidine, reduced while phenylephrine increased responses to trains of stimuli. 6 These results are discussed in relation to the nature of the innervation of rat vas deferens and the usefulness of the preparation in pharmacological tests for activity at a-adrenoceptors.

“…It has recently been demonstrated in principle that the sympathetic cardioaccelerator response in situ in the pithed rat can be potentiated by yohimbine or phentolamine (Docherty & McGrath, 1977a;Doxey, 1977).…”

Section: Introductionmentioning

confidence: 99%

An ANALYSIS OF SOME FACTORS INFLUENCINGα‐ADRENOCEPTOR FEED‐BACK AT THE SYMPATHETIC JUNCTION IN THE RAT HEART

Docherty

McGrath

1979

The effects of the selective prejunctional α‐adrenoceptor antagonist, yohimbine, on the cardio‐acceleration responses to sympathetic stimulation were examined in the pithed rat. Yohimbine reversed the inhibitory effects of the α‐adrenoceptor agonist, clonidine. on the stimulation‐induced tachycardia. Yohimbine failed to potentiate significantly responses to stimulation in the absence of clonidine when stimulation was applied at the optimal level for cardiac responses (C6‐T1). When the pithing rod electrode was moved to T2‐T6, cardioaccelerator responses were smaller and yohimbine produced potentiation at frequencies of ≥ 1 Hz. This potentiation was prejunctional since responses to exogenous noradrenaline (NA) were not increased by yohimbine. In the presence of cocaine, potentiation by yohimbine could be shown at the lower frequency of 0.1 Hz. The possible physiological significance of a negative feed‐back effect of noradrenaline on cardiac sympathetic nerves is discussed.