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      G Proteins and Endothelium-Dependent Relaxations

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          Abstract

          Endothelial cells control the tone of the underlying smooth muscle by releasing relaxing factors (nitric oxide, NO, prostacyclin and endothelium-derived hyperpolarizing factor). G proteins couple a number of endothelial cell receptors to the activation of NO synthase. Pertussis toxin selectively ADP-ribosy-lates certain G proteins (mainly G<sub>i</sub>). In the porcine coronary artery, pertussis toxin inhibits the release of NO evoked by certain (serotonin, α<sub>2</sub>-adrenergic agonists, leukotrienes, thrombin), but not all, (bradykinin, adenosine diphosphate) endothelium-dependent vasodilators. This suggests that both G<sub>i</sub> and G<sub>q </sub>proteins can couple receptor activation to the increase in endothelial Ca<sup>2+</sup> concentration required to stimulate NO synthase. In arteries with regenerated endothelium and in cultured endothelial cells, the release of NO evoked by pertussis-toxin-sensitive mechanisms is severely reduced or absent, while the response to other endothelium-dependent agonists is normal. To judge from experiments with cultured endothelial cells, the curtailment in pertussis-toxin-sensitive release of NO is due to an abnormal function rather than a reduced presence of G<sub>i</sub> proteins, or a reduced sensitivity of the cell membrane receptor. The selective impairment of G<sub>i</sub> proteins in regenerated endothelial cells predisposes the blood vessel wall to vasospasm and to the initiation of the atherosclerotic process.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1997
          1997
          24 September 2008
          : 34
          : 3
          : 175-185
          Affiliations
          aINSERM, Hôpital Lariboisière, Paris et bInstitut de Recherches Internationales Servier, Courbevoie, France
          Article
          159221 J Vasc Res 1997;34:175–185
          10.1159/000159221
          9226299
          © 1997 S. Karger AG, Basel

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          Page count
          Pages: 11
          Categories
          Introduction

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