Cardiovascular effects of 2-(<i>NN</i>-dimethyl)amino-6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene in pithed rats: differential antagonism by yohimbine and prazosin

1 The prejunctional inhibitory effects of clonidine and 6-fluoronoradrenaline (6-FNA) have been evaluated in the isolated prostatic segment of the rat vas deferens, against the twitch response evoked by low frequency (0.1 Hz) field stimulation.2 The inhibitory potency of 6FNA was significantly increased in the presence of cocaine (1 jtM) or pargyline (10 JM), but was not modified in the vas deferens from rats pretreated with reserpine when the endogenous levels ofnoradrenaline (NA) were decreased by 97%. Clonidine was significantly more potent than 6-FNA as an inhibitory agonist, and the potency of clonidine was not modified after cocaine, pargyline or reserpine. 3 The a2-adrenoceptor blocking agent idazoxan, was a competitive antagonist against the inhibitory effects of clonidine under all experimental conditions. In contrast, the only antagonism shown by idazoxan against the inhibitory effects of 6-FNA was in the presence of cocaine (1 JM), and this antagonist effect of idazoxan was not concentration-related. 4 Low concentrations of 6-FNA caused concentration-dependent facilitatory effects on the twitch response, which were significantly greater after treatment with idazoxan (1 I1M) in reserpine-treated vas deferens. These facilitatory effects of6-FNA were always observed in the presence ofprazosin (300 nM) and also after treatment of the preparations with phenoxybenzamine (10 I1M), a concentration which abolished the inhibitory actions of both clonidine and 6-FNA. The facilitatory effects on the twitch response induced by low concentrations of 6-FNA are therefore unlikely to be due to either a,-or x2-adrenoceptor stimulation. 5 In conclusion, the failure of idazoxan to block the inhibitory effects of 6-FNA, while exerting a potent competitive antagonism of clonidine-induced inhibitory effects, supports the proposal that a2-adrenoceptors may in fact be subdivided into two subclasses, involving imidazoline and phenylethylamine recognition sites.

Section: Discussionsupporting

confidence: 80%

Differential blocking actions of idazoxan against the inhibitory effects of 6‐fluoronoradrenaline and clonidine in the rat vas deferens

Hicks

Langer

Macrae

1985

“…It can thus be concluded that functional ax-adrenoceptors are present in freshly dispersed single smooth muscle cells from rat tail artery. Exposure to TL99, an M2-adrenoceptor agonist (Hicks & Cannon, 1980 In order to evaluate whether the enzymatic dispersal of the cells results in functional impairment, we compared the concentration and time-course response curves for cirazoline and TL99 obtained from freshly dispersed single cells to those from artery rings. Both the time-course and the concentration-response curves from isolated tissues and single cells were similar.…”

Section: Resultsmentioning

confidence: 99%

The effects of α‐adrenoceptor agonists on intracellular Ca²+ levels in freshly dispersed single smooth muscle cells from rat tail artery

Kargacin

Triggle

1993

1 The presence of functional x-adrenoceptors in freshly dispersed single smooth muscle cells from rat tail arteries was investigated by use of selective ax-adrenoceptor agonists and antagonists. 2 Cirazoline, a selective a,-adrenoceptor agonist, caused a prazosin-sensitive, rapid but transient increase in intracellular Ca2 , which was partially inhibited by the voltage-dependent Ca2+ channel blocker, nifedipine. 3 TL99, an a2-adrenoceptor agonist, in the presence of prazosin, initiated a slow and sustained increase in intracellular Ca2+ which was partially inhibited by yohimbine and almost completely blocked by nifedipine. 4 In rat tail artery, the effects (dose-response and time-response curves) of cirazoline and TL99 on intracellular Ca2+ levels in freshly dispersed single smooth muscle cells were comparable with those obtained with organ bath studies of ring preparations of artery. 5 In freshly dispersed single smooth muscle cells, the time-course response curves induced by the selective xl-adrenoceptor agonist, phenylephrine and the selective X2-adrenoceptor agonist, UK14304, were similar to those observed with cirazoline and TL99, respectively.6 These results indicate that: (a) functional al-and M2-adrenoceptors are present in freshly dispersed single smooth muscle cells from rat tail artery and (b) a,-and x2-adrenoceptors are coupled to different cellular processes that lead to an increase in intracellular Ca2 .

“…The most direct evidence for the presence of smooth muscle X2-adrenoceptors was the effect of the selective a2-adrenoceptor agonist TL99 (Hicks & Cannon, 1981): in SHR tail arteries, responses to TI99 were substantially reduced by idazoxan (100 nmol 1-'), unaffected by prazosin (1 nmol 11) and virtually abolished if the extracellular calcium concentration was halved . In contrast, responses to the selective ai-adrenoceptor agonist methoxamine were unaffected by idazoxan, markedly reduced by prazosin and unaffected by halving the calcium concentration ; thus both oi-and o2-adrenoceptors would appear to be present on smooth muscle cells in this vessel.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of both a1-and a2-subtypes on smooth muscle cells in rat tail arteries was reported in the latter studies, based on the effects of idazoxan (selective a2-adrenoceptor antagonist; Doxey et al, 1983) and prazosin (selective cx1-adrenoceptor antagonist) on responses to NA and to TL99 (selective a2-adrenoceptor agonist; Hicks & Cannon, 1981). In addition, the rat isolated tail artery is a stable and sensitive preparation with some of the characteristics of a true resistance vessel (Cheung, 1982a,b) and therefore, is particularly suitable for in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

Effects of reduced calcium ion concentration and of diltiazem on vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rat isolated tail artery

Medgett

Rajanayagam

1984

1 In isolated, perfused proximal segments of Sprague-Dawley rat tail artery, idazoxan (100 nmol 1-1) displaced the concentration-response curve to noradrenaline (NA) to the right. The log shift of the NA concentration-response curve was greater at lower concentrations than at higher concentrations of NA. Idazoxan (100 nmol 11) had no effect on responses to electrical stimulation.2 Prazosin (10 nmol 1-') displaced the concentration-response curve to NA to the right as well as markedly reducing responses to sympathetic nerve stimulation. 3 The concentration-response curve to NA, obtained after reducing the concentration of calcium ions in the Krebs solution from 2.5 to 0.6 mmol 1-', was significantly displaced to the right. Responses to sympathetic nerve stimulation were not affected by this reduction in the concentration of calcium ions.4 Diltiazem (1 and 10 pimol 11) significantly displaced the concentration-response curve to NA to the right but had no effect on sympathetic nerve stimulation. 5 These in vitro results in peripheral arterial smooth muscle confirm the findings of previous in vivo studies which suggest that aC2-adrenoceptors contribute to the vasoconstrictor responses elicited by cx-adrenoceptor agonists and that these responses but not those mediated by oti-adrenoceptors are dependent on extracellular calcium.