Differential response to chloroethylclonidine in blood vessels of normotensive and spontaneously hypertensive rats: role of α1D‐ and α1A‐adrenoceptors in …
British journal of pharmacology, 2000•Wiley Online Library
The effects of chloroethylclonidine on α1‐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.
Chloroethylclonidine elicited concentration‐dependent contractions. Maximal contraction
was similar in caudal arteries among strains (∼ 40% of noradrenaline effect). However,
chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive …
endothelium‐denuded caudal arteries and aorta from normotensive Wistar and Wistar Kyoto
(WKY), and from spontaneously hypertensive (SHR) rats were evaluated.
Chloroethylclonidine elicited concentration‐dependent contractions. Maximal contraction
was similar in caudal arteries among strains (∼ 40% of noradrenaline effect). However,
chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive …
- The effects of chloroethylclonidine on α1‐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.
- Chloroethylclonidine elicited concentration‐dependent contractions. Maximal contraction was similar in caudal arteries among strains (∼40% of noradrenaline effect). However, chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive rats. In Wistar aorta chloroethylclonidine produced the smallest contractile response.
- 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 effect.
- In chloroethylclonidine‐treated aorta noradrenaline elicited biphasic contraction‐response curves, indicating a high affinity (pD2, 8.5–7.5) chloroethylclonidine‐sensitive component and a low affinity (pD2, 6.3–5.2) chloroethylclonidine‐insensitive component. The high affinity component was blocked by chloroethylclonidine; while in caudal arteries noradrenaline elicited monophasic contraction‐response curves with pD2 values (6.5–5.7) similar to the low affinity component in aorta.
- Chloroethylclonidine inhibition of noradrenaline response was greater in aorta than in caudal arteries. Chloroethylclonidine increased the EC50 values of noradrenaline ∼1000 fold in aorta and ∼10 fold in caudal arteries.
- In SHR aorta BMY 7378 protected α1D‐adrenoceptors and in caudal arteries 5‐methylurapidil protected α1A‐adrenoceptors from chloroethylclonidine alkylation, allowing noradrenaline to elicit contraction.
- These results show marked strain‐dependent differences in the ability of chloroethylclonidine to contract aorta; moreover, chloroethylclonidine stimulates α1D‐adrenoceptors in aorta and α1A‐adrenoceptors in caudal arteries. The higher contraction observed in aorta from SHR and WKY suggests an augmented number of α1D‐adrenoceptors in these strains.
British Journal of Pharmacology (2000) 129, 653–660; doi:10.1038/sj.bjp.0703097
Wiley Online Library