Di(cid:128)erential response to chloroethylclonidine in blood vessels of normotensive and spontaneously hypertensive rats: role of a 1D - and a 1A -adrenoceptors in contraction

1 The e(cid:128)ects of chloroethylclonidine on a 1 -adrenoceptor-mediated contraction in endothelium- denuded caudal arteries and aorta from normotensive Wistar and Wistar Kyoto (WKY), and from spontaneously hypertensive (SHR) rats were evaluated. 2 Chloroethylclonidine elicited concentration-dependent contractions. Maximal contraction was similar in caudal arteries among strains ( & 40% of noradrenaline e(cid:128)ect). However, chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive rats. In Wistar aorta chloroethylclonidine produced the smallest contractile response. 3 In SHR aorta, BMY 7378 and 5-methylurapidil blocked chloroethylclonidine-elicited contraction, while (+)-cyclazocine did not inhibit it; while in caudal arteries, 5-methylurapidil blocked chloroethylclonidine action; the other antagonists had no e(cid:128)ect. 4 In chloroethylclonidine-treated aorta noradrenaline elicited biphasic contraction-response curves, indicating a high a(cid:129)nity (pD 2 , 8.5–7.5) chloroethylclonidine-sensitive component and a low a(cid:129)nity (pD 2 , 6.3–5.2) chloroethylclonidine-insensitive component. The high a(cid:129)nity component was blocked by chloroethylclonidine; while in caudal arteries noradrenaline elicited monophasic contraction-response curves with pD 2 values (6.5– 5.7) similar to the low a(cid:129)nity component in aorta. 5 Chloroethylclonidine inhibition of noradrenaline response was greater in aorta than in caudal arteries. Chloroethylclonidine increased the EC 50 values of noradrenaline & 1000 fold in aorta and & 10 fold in caudal arteries. 6 In SHR aorta BMY 7378 protected a 1D -adrenoceptors and in caudal arteries 5-methylurapidil protected a 1A -adrenoceptors from chloroethylclonidine alkylation, allowing noradrenaline to elicit contraction. 7 These results show marked strain-dependent di(cid:128)erences in the ability of chloroethylclonidine to contract aorta; moreover, chloroethylclonidine stimulates a 1D -adrenoceptors in aorta and a 1A adrenoceptors in caudal arteries. The higher contraction observed in aorta from SHR and WKY suggests an augmented number of a 1D -adrenoceptors in these strains. British Journal of Pharmacology (2000) 129, 653 –660

[1]  J. Nunes,et al.  Chloroethylclonidine irreversibly activates postjunctional alpha2-adrenoceptors in the dog saphenous vein , 1993, Naunyn-Schmiedeberg's Archives of Pharmacology.

[2]  R. Villalobos-Molina,et al.  Chloroethylclonidine is a partial alpha1-adrenoceptor agonist in aorta and caudal arteries of the Wistar Kyoto rat. , 1998, European journal of pharmacology.

[3]  G. Tsujimoto,et al.  Subtype-specific differences in subcellular localization of alpha1-adrenoceptors: chlorethylclonidine preferentially alkylates the accessible cell surface alpha1-adrenoceptors irrespective of the subtype. , 1997, Molecular pharmacology.

[4]  M. Piascik,et al.  Immunocytochemical localization of the alpha-1B adrenergic receptor and the contribution of this and the other subtypes to vascular smooth muscle contraction: analysis with selective ligands and antisense oligonucleotides. , 1997, The Journal of pharmacology and experimental therapeutics.

[5]  J. Docherty,et al.  Further investigation of the alpha-adrenoceptor-mediated actions of chloroethylclonidine in rat aorta. , 1997, European journal of pharmacology.

[6]  G. Janssen,et al.  α1-Adrenoceptor subtypes in rat aorta and mesenteric small arteries are preserved during left ventricular dysfunction post-myocardial infarction , 1997 .

[7]  A. Ford,et al.  Pharmacological characterization of an α1A‐adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat , 1997, British journal of pharmacology.

[8]  A. Hancock.  α1 Adrenoceptor subtypes: A synopsis of their pharmacology and molecular biology , 1996 .

[9]  R. Villalobos-Molina,et al.  α1-Adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the α1D or α1A subtypes , 1996 .

[10]  N. Kanagy,et al.  Increased responsiveness and decreased expression of G proteins in deoxycorticosterone hypertension. , 1996, Hypertension.

[11]  H. Kato,et al.  Adrenoceptors in SHR: alterations in binding characteristics and intracellular signal transduction pathways. , 1995, Life sciences.

[12]  R. Graham,et al.  Constitutive activation of a single effector pathway: evidence for multiple activation states of a G protein-coupled receptor. , 1996, Molecular pharmacology.

[13]  G. Tsujimoto,et al.  Selectivity of the imidazoline α‐adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned α1‐adrenoceptor subtypes , 1995 .

[14]  J. Docherty,et al.  Investigation of the actions of chloroethylclonidine in rat aorta , 1995, British journal of pharmacology.

[15]  A. Naylor,et al.  Characterization of an α1D‐adrenoceptor mediating the contractile response of rat aorta to noradrenaline , 1995, British journal of pharmacology.

[16]  A. Goetz,et al.  BMY 7378 is a selective antagonist of the D subtype of α1-adrenoceptors , 1995 .

[17]  A. Goetz,et al.  BMY 7378 is a selective antagonist of the D subtype of alpha 1-adrenoceptors. , 1995, European journal of pharmacology.

[18]  K. Minneman,et al.  Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. , 1994, Molecular pharmacology.

[19]  D. Harder,et al.  Guanine nucleotide-binding proteins in aortic smooth muscle from hypertensive rats. , 1994, Hypertension.

[20]  K. Starke,et al.  Chloroethylclonidine: an irreversible agonist at prejunctional α2‐adrenoceptors in rat vas deferens , 1993, British journal of pharmacology.

[21]  M. Oriowo,et al.  Heterogeneity of postjunctional alpha 1-adrenoceptors in mammalian aortae: subclassification based on chlorethylclonidine, WB 4101 and nifedipine. , 1992, Journal of vascular research.

[22]  I. Muramatsu,et al.  Subtypes of alpha 1-adrenoceptors involved in noradrenaline-induced contractions of rat thoracic aorta and dog carotid artery. , 1991, Japanese journal of pharmacology.

[23]  K. Minneman,et al.  Subtypes of α1adrenoceptors in rat blood vessels , 1990 .

[24]  P. Abel,et al.  Comparison of alpha 1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101. , 1988, Molecular pharmacology.

[25]  P. Abel,et al.  Heterogeneity of alpha 1-adrenergic receptors revealed by chlorethylclonidine. , 1987, Molecular pharmacology.

[26]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[27]  R. Ruffolo,et al.  Receptor interactions of imidazolines. IV. Structural requirements for alpha adrenergic receptor occupation and receptor activation by clonidine and a series of structural analogs in rat aorta. , 1980, The Journal of pharmacology and experimental therapeutics.

[28]  C. Wermuth,et al.  STUDIES ON SOME para‐SUBSTITUTED CLONIDINE DERIVATIVES THAT EXHIBIT AN α‐ADRENOCEPTOR STIMULANT ACTIVITY , 1980, British journal of pharmacology.