Inhibition of endothelium‐dependent hyperpolarization by endothelial prostanoids in guinea‐pig coronary artery

• Published in: British journal of pharmacology 1999-01, Vol.126 (1), p.1-10
• Main Authors: Yajima, Kazuhiro, Nishiyama, Makoto, Yamamoto, Yoshimichi, Suzuki, Hikaru
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Antihypertensive Agents - pharmacology; autoregulation; Benzopyrans - pharmacology; Biological and medical sciences; Blood vessels and receptors; Cell Membrane - drug effects; Cell Membrane - physiology; coronary artery; Coronary Vessels - drug effects; Coronary Vessels - physiology; Cyclooxygenase Inhibitors - pharmacology; Diclofenac - pharmacology; Dose-Response Relationship, Drug; EDHF; Electric Conductivity; endothelium; Endothelium, Vascular - physiology; Epoprostenol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; hyperpolarization; In Vitro Techniques; Male; Membrane Potentials - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; PGI2; Potassium - pharmacology; Prostaglandins - pharmacology; Reproducibility of Results; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702254

In smooth muscle of the circumflex coronary artery of guinea‐pig, acetylcholine (ACh, 10−6 M) produced an endothelium‐dependent hyperpolarization consisting of two components. An initial component that occurs in the presence of ACh and a slow component that developed after ACh had been withdrawn. Each component of the hyperpolarization was accompanied by an increase in membrane conductance. Indomethacin (5×10−6 M) or diclofenac (10−6 M), both inhibitors of cyclooxygenase, abolished only the slow hyperpolarization. The initial hyperpolarization was not inhibited by diclofenac nor by nitroarginine, an inhibitor of nitric oxide synthase. Both components of the ACh‐induced hyperpolarization were abolished in the presence of atropine (10−6 M) or high‐K solution ([K+]0=29.4 mM). The interval between ACh‐stimulation required to generate an initial hyperpolarization of reproducible amplitude was 20 min or greater, but it was reduced to less than 5 min after inhibiting cyclooxygenase activity. Conditioning stimulation of the artery with substance P (10−7 M) also caused a long duration (about 20 min) inhibition of the ACh‐response. The amplitude of the hyperpolarization generated by Y‐26763, a K+‐channel opener, was reproducible within 10 min after withdrawal of ACh. Exogenously applied prostacyclin (PGI2) hyperpolarized the membrane and reduced membrane resistance in concentrations over 2.8×10−9M. At concentrations below threshold for hyperpolarization and when no alteration of membrane resistance occurred, PGI2 inhibited the initial component of the ACh‐induced hyperpolarization. It is concluded that endothelial prostanoids, possibly PGI2, have an inhibitory action on the release of endothelium‐derived hyperpolarizing factor. British Journal of Pharmacology (1999) 126, 1–10; doi:10.1038/sj.bjp.0702254