Differential response to chloroethylclonidine in blood vessels of normotensive and spontaneously hypertensive rats: role of alpha(1D)- and alpha(1A)-adrenoceptors in contraction

1 The effects of chloroethylclonidine on alpha(1)-adrenoceptor-mediated con traction in endothelium-denuded caudal arteries and aorta from normotensive Wistar and Wistar Kyoto (WKY), and from spontaneously hypertensive (SHR) r ats were evaluated. 2 Chloroethylclonidine elicited concentration-dependent contractions. Maxim al contraction was similar in caudal arteries among strains (approximate to 40% of noradrenaline effect). However, chloroethylclo nidine elicited a hi gher contraction in aorta from SHR than from normotensive rats. In Wistar a orta 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 ca udal arteries, 5-methylurapidil blocked chloroethylclonidine action; the ot her antagonists had no effect. 4 In chloroethylclonidine-treated aorta noradrenaline elicited biphasic con traction-response curves, indicating a high affinity (pD(2), 8.5-7.5) chlor oethylclonidine-sensitive component and a low affinity (pD(2), 6.3-5.2) chl oroethylclonidine-insensitive component. The high affinity component was bl ocked by chloroethylclonidine; while in caudal arteries noradrenaline elici ted monophasic contraction-response curves with pD(2) values (6.5-5.7) simi lar to the low affinity component in aorta. 5 Chloroethylclonidine inhibition of noradrenaline response was greater in aorta than in caudal arteries. Chloroethylclonidine increased the EC50 valu es of noradrenaline approximate to 1000 fold in aorta and approximate to 10 fold in caudal arteries. 6 In SHR aorta BMY 7378 protected alpha(1D)-adrenoceptors and in caudal art eries 5-methylurapidil protected alpha(1A)-adrenoceptors from chloroethylcl onidine alkylation, allowing noradrenaline to elicit contraction. 7 These results show marked strain-dependent differences in the ability of chloroethylclonidine to contract aorta; moreover, chloroethylclonidine stim ulates alpha(1D)-adrenoceptors in aorta and alpha(1A)-adrenoceptors in caud al arteries. The higher contraction observed in aorta from SHR and WKY sugg ests an augmented number of alpha(1D)-adrenoceptors in these strains.