| Autor: |
Márton Z; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Pataricza J; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Pollesello P; Orion Pharma, Espoo, Finland., Varró A; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Papp JG; MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2019 Sep; Vol. 74 (3), pp. 218-224. |
| DOI: |
10.1097/FJC.0000000000000700 |
| Abstrakt: |
Relaxation and changes in the transmembrane potential of vascular smooth muscle induced by ORM-3819, a novel inodilating compound, were investigated in isolated porcine coronary arteries. Isometric tone was studied on arterial rings precontracted by KCl (30 mM), and resting membrane potential was investigated by a conventional microelectrode technique. ORM-3819 in the concentration range 0.38-230.6 µM evoked concentration-dependent relaxation with a maximum value of 58.1% and an effective concentration of the relaxing substance that caused 50% of maximum relaxation of 72.2 µM. The maximum hyperpolarization produced by ORM-3819 at a concentration of 120 µM (-2.6 ± 0.81 mV, N = 10) did not differ significantly from that induced by C-type natriuretic peptide (CNP), an endogenous hyperpolarizing mediator, at a concentration of 1.4 µM (-3.6 ± 0.38 mV, N = 17). The same effect elicited by the known inodilator levosimendan was less pronounced at a concentration of 3.7 µM: -1.82 ± 0.44 mV, N = 22 (P < 0.05 vs. CNP). The voltage-gated potassium channel inhibitor 4-aminopyridine, at a concentration of 5 mM, attenuated the relaxation induced by ORM-3819 at concentrations of 41.6 or 117.2 µM. These results suggest that ORM-3819 is a potent vasodilating agent able to relieve coronary artery vasospasm by causing hyperpolarization of vascular smooth muscle cells through processes involving activation of voltage-gated potassium channels. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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