Summary
The effects of the selective α-adrenoceptor antagonists idazoxan (α2) and prazosin (α1) were examined on responses to exogenous noradrenaline and to sympathetic nerve stimulation in SHR and WKY rat isolated perfused proximal tail artery segments. The influence of inhibition of neuronal uptake with cocaine on the effects of these antagonists was also determined. The following results were obtained.
-
1.
Prazosin (10 nmol/l) was equieffective in antagonising responses to exogenous noradrenaline and sympathetic nerve stimulation in both SHR and WKY arteries and the degree of antagonism was similar in either the presence or the absence of neuronal uptake inhibition.
-
2.
In contrast to prazosin, the effects of idazoxan (100 nmol/l), on both exogenous noradrenaline and sympathetic nerve stimulation were dependent on the degree of inhibition of neuronal uptake.
-
3.
In SHR arteries, the degree of antagonism of responses to exogenous noradrenaline by idazoxan (100 nmol/l) decreased progressively as the concentration of cocaine was increased to 4 and 40 μmol/l; in WKY arteries, even in the absence of cocaine, idazoxan (100 nmol/l) did not antagonise responses to exogenous noradrenaline.
-
4.
In SHR arteries, the responses to sympathetic nerve stimulation were reduced to a lesser extent by idazoxan (100 nmol/l) when the concentration of cocaine was increased to 4 μmol/l than in the absence of cocaine. In WKY arteries, idazoxan (100 nmol/l) reduced the responses to sympathetic nerve stimulation in the absence of cocaine. However, this concentration of idazoxan increased the responses to nerve stimulation in the presence of cocaine.
-
5.
Our results indicate that smooth muscle α2-adrenoceptors are present in SHR tail arteries, both intra-and extrajunctionally. It appears that these postjunctional α2-adrenoceptors are distributed unevenly across the vessel wall, with the density of α2-adrenoceptors being greater close to the lumen. By increasing the access of noradrenaline to the adventitial-medial border region where α1-adrenoceptors predominate, cocaine decreases the relative contribution of postjunctional α2-adrenoceptors to responses to both exogenous and endogenous noradrenaline.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Collis MG, Vanhoutte PM (1977) Vascular reactivity of isolated perfused Kidneys from male and female spontaneously hypertensive rats. Circ Res 41:759–767
Doxey JC, Roach AG, Smith CFC (1983) Studies on RX 781094, a selective potent specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–506
Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Catecholamines. Springer, Berlin Heidelberg New York, pp 283–335
Granata AR, Enero MA, Krieger EM, Langer SZ (1983) Norepinephrine release and vascular response elicited by nerve stimulation in rats with chronic neurogenic hypertension. J Pharmacol Exp Ther 227:187–193
Hicks PE, Cannon JG (1981) Cardiovascular effects of 2-(N,N-dimethyl)-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene in the pithed rat. Differential antagonism by yohimbine and prazosin. J Pharm Pharmacol 32:786–790
Hicks PE, Langer SZ, Medgett IC (1983) Greater contribution of smooth muscle Studies on RX 781094, a selective potent specific antagonist of α2-adrenoceptors to vasoconstrictor responses in SHR than in WKY rat tail arteries. Br J Pharmacol 79:230P
Hicks PE, Medgett IC, Langer SZ (1984) Postsynaptic α2-adrenergic receptor mediated vasoconstriction in SHR tail arteries in vitro. Hypertension 6:I12-I18
Langer SZ (1974) Presynaptic regulation of catecholamine release. Biochem Pharmacol 23:1793–1800
Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Langer SZ, Medgett IC (1983) Subclassification of smooth muscle α-adrenoceptors of the rat tail artery. Br J Pharmacol 78: 44P
Langer SZ, Shepperson MB (1982) Recent developments in vascular smooth muscle pharmacology: the postsynaptic α2-adrenoceptors. Trends Pharmacol Sci 3:440–444
Langer SZ, Massingham R, Shepperson NB (1980) Presence of postsynaptic α2-adrenoceptors of predominantly extrasynaptic location in the vascular smooth muscle of the dog hind limb. Clin Sci 59:225s-228s
Langer SZ, Shepperson NB, Massingham R (1981) Preferential noradrenergic innervation of α1-adrenergic receptors in vascular smooth muscle. Hypertension (suppl 1) 3:I112-I118
Langer SZ, Duval N, Massingham R (1985) Pharmacological and therapeutic significance of alpha-adrenoceptor subtypes. J Cardiovasc Pharmacol (in press)
Limberger N, Starke K (1983) Partial agonist effect of 2-[2-(1,4-benzodioxanyl)]-2-imidazoline (RX 781094) at presynaptic α2-adrenoceptors in rabbit ear artery. Naunyn-Schmiedeberg's Arch Pharmacol 324:75–78
McGrath JC (1982) Evidence for more than one type of postjunctional α-adrenoceptor. Biochem Pharmacol 31:467–484
Medgett IC, Langer SZ (1983) Characterisation of smooth muscle α-adrenoceptors and of responses to electrical stimulation in the cat isolated perfused middle cerebral artery. Naunyn-Schmiedeberg's Arch Pharmacol 323:24–32
Medgett IC, Langer SZ (1984) Heterogeneity of smooth muscle α-adrenoceptors in the rat tail artery in vitro. J Pharmacol Exp Ther 229:823–830
Medgett IC, Rand MJ (1981) Dual effects of clonidine on rat prejunctional α-adrenoceptors. Clin Exp Pharmacol Physiol 8:503–507
Medgett IC, Hicks PE, Langer SZ (1984) Smooth muscle α2-adrenoceptors mediate vasoconstrictor responses to exogenous norepinephrine and to sympathetic stimulation to a greater extent in SHR than in WKY rat tail arteries. J Pharmacol Exp Ther 231:159–165
Ruffolo RR, Yaden EL (1984) The existence of spare α2-adrenoceptors but not α2-adrenoceptors, for the respective vasopressor effects of cirazoline and B-HT 933 in pithed rat. J Cardiovasc Pharmacol 6:1011–1019
Skärby T, Andersson K-E, Edvinsson L (1981) Characterisation of the postsynaptic α-adrenoceptor in isolated feline cerebral arteries. Acta Physiol Scand 112:105–107
Stephens MK, Moulds RFW (1981) Heterogenicity of postjunctional α-adrenoceptors in human vascular smooth muscle. Arch Int Pharmacodyn 254:43–57
Timmermans PBMWM, Van Zwieten PA (1981) Minireview: The postsynaptic α2-adrenoceptors. J Auton Pharmacol 7:171–183
Van Brummelen P, Vermey P, Timmermans PBMWM, Van Zwieten PA (1983) Preliminary evidence for a postsynaptic α2-adrenoceptors in the vasculature of the human forearm. Br J Clin Pharmacol 15:134
Webb RC, Vanhoutte PM, Bohr DF (1981) Adrenergic neurotransmission in vascular smooth muscle from spontaneously hypertensive rats. Hypertension 3:93–103
Winquist RJ, Webb RC, Bohr DF (1982) Vascular smooth muscle in hypertension. Fed Proc 41:2387–2393
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Medgett, I.C., Langer, S.Z. Influence of neuronal uptake on the contribution of smooth muscle α2-adrenoceptors to vasoconstrictor responses to noradrenaline in SHR and WKY isolated tail arteries. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 43–49 (1986). https://doi.org/10.1007/BF00633195
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00633195