Ranolazine enhances nicardipine-induced relaxation of alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta
Malavaki, C. J., Hatziefthimiou, A, Daskalopoulou, S, Stefanidis, I, Karatzaferi, Christina and Aidonidis, I (2014) Ranolazine enhances nicardipine-induced relaxation of alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta. Acta Cardiologica, 70 (2). pp. 157-162. ISSN 0001-5385
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Ranolazine (RAN) and nicardipine (NIC) have been studied for their vasorelaxing effects but the combination of these agents against adrenergic vasoconstriction has not been tested. The present study aimed at investigating the vasorelaxing effect by the combination of the two agents on alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta. Aortic rings were mounted for isometric tension recording in organ baths containing Krebs-Henseleit solution. Concentration-response curves of RAN (10–9 to 10–4 M), NIC (10–9 to 10–5 M), and RAN + NIC (3 × 10–6 M) were obtained in a cumulative manner using phenylephrine (PE, 2 × 10–6 M) as constrictor agent. The effective concentration (EC)50 values for RAN and NIC were 6.5 × 10–6 M and 1.4 × 10–5 M, respectively. The treatment of PE-precontracted aortic rings with either RAN or NIC up to 65 min revealed that both agents displayed a biphasic pattern of initial rising and late sustained phases of relaxation. At 35 min of incubation, RAN and NIC induced relaxation by 23 ± 3% and 14 ± 4%, respectively (N = 7, P = NS, RAN vs NIC); their combination resulted in a 34 ± 4% relaxation (N = 7; P < 0.01, RAN + NIC vs NIC). At 65 min the effect of NIC prevailed and tended to be closer to the values of the combination treatment (P < 0.01, RAN + NIC vs RAN). The results indicate that RAN at therapeutic concentrations exerts a significant additive vasorelaxing effect when combined with NIC in rabbit aorta.
| Item Type: | Article |
|---|---|
| Additional Information: | Article can be freely downloaded from the link above |
| Keywords: | rabbit aorta, alpha1, adrenoceptor, vasorelaxation, randazine, nicardipine |
| Divisions: | ?? UniversityCollegePlymouthMarkJohn ?? |
| Depositing User: | Users 134 not found. |
| Date Deposited: | 23 Feb 2017 13:25 |
| Last Modified: | 22 May 2019 11:50 |
| URI: | https://marjon.repository.guildhe.ac.uk/id/eprint/15388 |
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