January 1999, Volume 126, Issue 1, Pages 1 - 10

Original Article

Inhibition of endothelium-dependent hyperpolarization by endothelial prostanoids in guinea-pig coronary artery Kazuhiro Yajima, Makoto Nishiyama, Yoshimichi Yamamoto & Hikaru Suzuki1 Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan     1Author for correspondence: E-mail: hisuzuki@med.nagoya-cu.ac.jp

Keywords

PGI2;   EDHF;   autoregulation;   hyperpolarization;   coronary artery;   endothelium

Abstract

1   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 An initial component that occurs in the presence of ACh and a slow component that developed after ACh had been withdrawn.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. 2   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. 3   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). 4   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. 5   The amplitude of the hyperpolarization generated by Y-26763, a K+-channel opener, was reproducible within 10 min after withdrawal of ACh. 6   Exogenously applied prostacyclin (PGI2) hyperpolarized the membrane and reduced membrane resistance in concentrations over 2.8×10-9M. 7   At concentrations below threshold for hyperpolarization and when no alteration of membrane resistance occurred, PGI2 inhibited the initial component of the ACh-induced hyperpolarization. 8   It is concluded that endothelial prostanoids, possibly PGI2, have an inhibitory action on the release of endothelium-derived hyperpolarizing factor.

Received 4 August 1998; Revised 16 September 1998; Accepted 28 September 1998

^© Macmillan Publishers Ltd 1999