Some electrical properties of the endothelium-dependent hyperpolarization recorded from rat arterial smooth muscle...

1. Electrical responses produced by acetylcholine (ACh) and histamine were recorded from smooth muscle cells of the intralobular small pulmonary artery (SPA), main pulmonary artery (MPA) and thoracic aorta of rats. 2. In MPA and SPA, ACh and histamine produced a transient hyperpolarization of the membrane, and the potential decayed exponentially with a time constant of 2-3 min. In aorta, ACh produced a sustained and histamine produced a transient hyperpolarization. 3. The ACh- and histamine-induced hyperpolarizations were blocked by atropine and mepyramine, respectively, or by removing the endothelial cells. 4. The amplitude of the hyperpolarization was increased in low [K+]o solutions and decreased in high [K+]o solutions. The ionic conductance of the membrane was increased during the hyperpolarization, suggesting an involvement of the increased potassium conductance. 5. A reproducible amplitude of hyperpolarization was generated when ACh or histamine was applied at intervals of over 10 or 30 min, respectively. 6. In aorta, after the transient hyperpolarization had ceased during continued application of histamine, ACh again produced a hyperpolarization, i.e. the transient nature of the hyperpolarization was not due to desensitization of the receptor upon which the hyperpolarizing substance acted, assuming histamine and ACh release the same hyperpolarizing substance. 7. ACh and histamine relaxed the tissues from SPA, MPA and aorta during the noradrenaline (NA)- or high [K+]o solution-induced contraction, in a concentration-dependent manner, only when the endothelial cells were intact. Both ACh and histamine were potent relaxants in MPA and aorta, but showed weak relaxing actions in SPA. 8. In aorta, ACh and histamine produced a sustained relaxation for up to 10 min, and Methylene Blue diminished and altered it to a transient relaxation (for histamine) or an initial large, followed by a small sustained (for ACh), relaxation. 9. In the presence of NA and NA plus Methylene Blue, ACh and histamine also produced a hyperpolarization similar to that seen in the control. 10. It is concluded that in arteries of the rat, ACh and histamine release a hyperpolarizing substance from the endothelial cells. This substance may be different from the endothelium-derived relaxing factor (EDRF), and is released mainly transiently. The hyperpolarization is generated by an increase in potassium conductance of the membrane, and this has some contribution to the endothelium-dependent relaxation.