Figure 1.

Endothelium‐derived vasoactive substances. Nitric oxide (NO) is released from endothelial cells in response to shear stress and activation of a variety of receptors. NO exerts vasodilating and antiproliferative effects on smooth muscle cells and inhibits thrombocyte aggregation and leukocyte adhesion. Endothelin‐1 (ET‐1) exerts its major vascular effects—vasoconstriction and cell proliferation—through activation of specific endothelin‐A (ET_A) receptors on vascular smooth muscle cells. In contrast, endothelin B (ET_B) receptors mediate vasodilation via release of NO and prostacyclin. In addition, ETB receptors in the lung were shown to be a major pathway for the clearance of ET‐1 from plasma. AI indiBcates angiotensin I; AII, angiotensin II; Thr, thrombine; TGFBβ₁, transforming growth factor β; AcCh, acetylcholine; 5‐HT, 5‐hydroxytryptamine (serotonin); ADP, adenosine diphosphate; BK, bradykinin; ACE, angiotensin‐converting enzyme; AT1, angiotensin II type 1 receptor; T, thromboxane receptor; bET‐1, big ET‐1; ECE, endothelin‐converting enzyme; M, muscarinergic receptor; S₁, serotoninergic receptor; B₂, bradykinin receptor; NOS, NO synthase; L‐Arg, L‐arginine; EDHF, endothelium‐derived hyperpolarizing factor; TXA₂, thromboxane; PGH₂, prostaglandin H₂; PGI₂, prostacyclin; cAMP, cyclic adenosine monophosphate; and cGMP, cyclic 3′,5′‐guanosine monophosphate. Adapted from Lülscher et al. ¹⁰⁷