Electrotonic propagation of kinin-induced, endothelium-dependent hyperpolarizations in pig coronary smooth muscles.

The kinins, substance P and bradykinin, cause endothelium-dependent hyperpolarizations in smooth muscles of the pig coronary artery. We tested whether the propagation, in the media, of these hyperpolarizations is passive or whether the hyperpolarizations are regenerated in the smooth muscle cells. The space constants measured in response to the kinin endothelium-dependent stimulations were compared to those obtained by electrical field stimulation. The space constant is 2.6 +/- 0.2 mm (n = 13) measured for substance P and 2.2 +/- 0.2 mm (n = 12) for bradykinin. The space constants established by electrical field stimulation-induced hyperpolarization are 3 +/- 0.2 mm (n = 7) for strips with intact endothelium and 2.7 +/- 0.3 mm (n = 7) for strips with removed endothelium. These results show that the space constants obtained for the kinin stimulations are not larger than those caused by electrical field stimulation. This suggests that the kinin-induced hyperpolarizations propagate, in the media, in a passive, electronic manner, therefore the hypothesis of regenerated kinin hyperpolarizations is unlikely.

Bidirectional electrical communication between smooth muscle and endothelial cells in the pig coronary artery.

Using strips of the left descending branch of the pig coronary artery in vitro, we show that smooth muscle cells are hyperpolarized by isoproterenol, a beta-agonist, independently of the presence or absence of intact endothelium. This hyperpolarization is transmitted to the lining endothelial cells in intact coronary strips. On the contrary, the cultured endothelial cells, without contact with smooth muscles, are not hyperpolarized by the beta-agonist. This shows that, in addition to the hyperpolarizations that flow from the endothelium to the media in response to kinins, electrical signals are also transmitted in the opposite direction, from the smooth muscles to the lining endothelial cells. In an attempt to test whether electrical coupling through gap junctions is implicated in the transmission of hyperpolarizations between the endothelial and the smooth muscle cells, we used halothane, a gap junction uncoupler. We observed that halothane does not inhibit the transmission of kinin hyperpolarizations from the endothelium to the smooth muscles, whereas it inhibits the transmission of isoproterenol hyperpolarization in the reverse direction.

Effect of nitro-L-arginine on endothelium-dependent hyperpolarizations and relaxations of pig coronary arteries.

1. Endothelium-dependent relaxation is caused by an endothelium-derived relaxing factor (EDRF) identified as nitric oxide (NO). Our objective was to test whether one or several distinct endothelium-dependent relaxing factors exist. 2. In pig coronary arteries, a hyperpolarization accompanied by the relaxation caused by high concentrations of substance P (SP) and bradykinin (BK). 3. To examine the role played by nitric oxide and prostacyclin in the endothelium-dependent relaxations and hyperpolarizations caused by SP and BK on pig coronary arterial strips, the production of NO was inhibited by NG-nitro-L-arginine (L-NNA) and the production of prostacyclin was inhibited by indomethacin, while monitoring smooth muscle membrane potential and isometric tension. 4. Indomethacin had no effect on resting isometric tension nor on SP and BK relaxations of strips precontracted by prostaglandin F2 alpha. 5. L-NNA contracted arterial strips with intact endothelium, without changing the membrane potential of smooth muscles. 6. The inhibitor shifted to the right the concentration-response curve of kinins by 0.2 nM SP and 20 nM BK. It inhibited the maximal relaxations and hyperpolarizations by 30%. 7. The results show that, in pig coronary arteries, EDRF (NO) mainly controls the basal tension, whereas other factor(s) play(s) an important role in hyperpolarizations and relaxations caused by the kinins.