Abstract
The endothelium relaxes vascular smooth muscle cells through at least three factors: nitric oxide (NO), prostacyclin (PGI~2~), and endothelium‐derived hyperpolarizing factor (EDHF). In the coronary circulation, we have conducted a series of experiments to study: 1) the inhibitory effects of NOS on the production of NO under stimulated status; 2) whether EDHF plays a role in either large or microarteries; 3) the cellular membrane potential hyperpolarization linked with relaxation; 4) the potassium channels involved in EDHF‐mediated relaxation and hyperpolarization; and 5) EDHF‐function related to open‐heart surgery. In porcine coronary arteries, NO release was directly measured by electrochemical methods using an NO‐specific electrode and an NO meter. The cellular membrane potential of smooth muscle cells was measured electrophysiologically by using a microelectrode in both large and small coronary arteries. Isometric force recording was used to study relaxations in organ chambers for large arteries and in myograph for microarteries. This article reviews these aspects. A) In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5±2.4 nM to 105.0±19.6 nM and hyperpolarization. L‐NNA treatment significantly reduced the BK‐stimulated rise in [NO] to 32.1±11.3 nM but did not affect hyperpolarization. B) Oxyhemoglobin eliminated indomethacin and L‐NNA‐resistant rise in [NO] but not relaxation (42.3±4.4%) and repolarization (−40±2 mV) by BK. C) Tetraethylammonium, charybdotoxin, iberiotoxin, and apamin, used alone or in combination, partially decreased the BK‐induced responses. D) EDHF‐mediated relaxation and hyperpolarization are reduced by exposure to hyperkalemic cardioplegia. We conclude: i) that in porcine coronary large and microarteries, both EDHF and NO play important role in the endothelium‐dependent relaxation; ii) that NOS inhibitors reduce but do not completely eliminate NO production; iii) that Ca^2+^‐activated K^+^ channels (BK~Ca~ and SK~Ca~) play an important role in mediating the BK‐induced responses; and iv) that EDHF‐function can be protected by pharmacological methods. Drug. Dev. Res. 58:23–27, 2003. © 2003 Wiley‐Liss, Inc.