| First Author | Zhu QM | Year | 1999 |
| Journal | Br J Pharmacol | Volume | 126 |
| Issue | 6 | Pages | 1522-30 |
| PubMed ID | 10217548 | Mgi Jnum | J:56221 |
| Mgi Id | MGI:1340440 | Doi | 10.1038/sj.bjp.0702429 |
| Citation | Zhu QM, et al. (1999) Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol 126(6):1522-30 |
| abstractText | 1. We investigated the cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A- adrenoceptor mice. The in vitro pharmacology of these agonists was determined at recombinant (human) alpha2-adrenoceptors and at endogenous (dog) alpha2A-adrenoceptors. 2. In wild-type mice, rilmenidine, moxonidine (100, 300 and 1000 microg kg(-1), i.v.) and clonidine (30, 100 and 300 microg kg(-1), i.v.) dose-dependently decreased blood pressure and heart rate. 3. In D79N alpha2A- adrenoceptor mice, responses to rilmenidine and moxonidine did not differ from vehicle control. Clonidine-induced hypotension was absent, but dose-dependent hypertension and bradycardia were observed. 4. In wild-type mice, responses to moxonidine (1 mg kg(-1), i.v.) were antagonized by the non-selective, non-imidazoline alpha2-adrenoceptor antagonist, RS-79948-197 (1 mg kg(-1), i.v.). 5. Affinity estimates (pKi) at human alpha2A-, alpha2B- and alpha2C-adrenoceptors, respectively, were: rilmenidine (5.80, 5.76 and 5.33), moxonidine (5.37, <5 and <5) and clonidine (7.21, 7.16 and 6.87). In a [35S]- GTPgammaS incorporation assay, moxonidine and clonidine were alpha2A- adrenoceptor agonists (pEC50/intrinsic activity relative to noradrenaline): moxonidine (5.74/0.85) and clonidine (7.57/0.32). 6. In dog saphenous vein, concentration-dependent contractions were observed (pEC50/intrinsic activity relative to noradrenaline): rilmenidine (5.83/0.70), moxonidine (6.48/0.98) and clonidine (7.22/0.83). Agonist- independent affinities were obtained with RS-79948-197. 7. Thus, expression of alpha2A-adrenoceptors is a prerequisite for the cardiovascular effects of moxonidine and rilmenidine in conscious mice. There was no evidence of I1-imidazoline receptor-mediated effects. The ability of these compounds to act as alpha2A-adrenoceptor agonists in vitro supports this conclusion. |
