The Novel Inodilator ORM-3819 Relaxes Isolated Porcine Coronary Arteries: Role of Voltage-Gated Potassium Channel Activation

Zoltán Márton, J. Pataricza, Piero Pollesello, A. Varró, J. Papp

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)218-224
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume74
Issue number3
DOIs
Publication statusPublished - Sep 1 2019

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C-Type Natriuretic Peptide
Voltage-Gated Potassium Channels
Vascular Smooth Muscle
Membrane Potentials
Coronary Vessels
Swine
Coronary Vasospasm
4-Aminopyridine
Microelectrodes
Smooth Muscle Myocytes
simendan

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

The Novel Inodilator ORM-3819 Relaxes Isolated Porcine Coronary Arteries : Role of Voltage-Gated Potassium Channel Activation. / Márton, Zoltán; Pataricza, J.; Pollesello, Piero; Varró, A.; Papp, J.

In: Journal of cardiovascular pharmacology, Vol. 74, No. 3, 01.09.2019, p. 218-224.

Research output: Contribution to journalArticle

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