Thorin E, Parent R, Ming Z, Lavallée M
Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal H3C 3J7, Montréal, Québec, Canada H1T 1C8.
Am J Physiol. 1999 Aug;277(2):H524-32. doi: 10.1152/ajpheart.1999.277.2.H524.
Nitric oxide (NO) may normally impair endothelin (ET) activity in epicardial coronary arteries. Lifting this inhibitory feedback could reveal ET-dependent effects involving ET(A)- and/or ET(B)-receptor activation. In conscious dogs, the blockade of ET(A) receptors (intracoronary Ro-61-1790) increased external circumflex coronary artery diameter (CD) (sonomicrometry) by 0.10 +/- 0.01 from 3.04 +/- 0.12 mm (P < 0.01) without altering coronary blood flow (Doppler). Similarly, CD increased (0.09 +/- 0.01 from 2.91 +/- 0.14 mm; P < 0. 01) when Ro-61-1790 was given after blockade of NO formation with intracoronary N(omega)-nitro-L-arginine methyl ester (L-NAME). In contrast, ET(B)-receptor blockade (intracoronary Ro-46-8443) did not influence baseline CD with and without L-NAME. In vitro, increases in tension caused by N(omega)-nitro-L-arginine (L-NNA) or PGF(2alpha) in arterial rings were reduced by ET(A)- but not ET(B)-receptor blockade. ET(A)-receptor blockade also reduced the increase in tension caused by L-NNA in human coronary arterial rings. Thus ET(A) receptors, but not ET(B) receptors, account for ET-dependent constriction in canine epicardial coronary arteries in vivo. ET-dependent effects were independent of the level of NO formation in vitro and in vivo. In human epicardial coronary arterial rings, ET(A)-receptor blockade also caused significant relaxation.
一氧化氮（NO）通常可能会削弱心外膜冠状动脉中内皮素（ET）的活性。解除这种抑制性反馈可能会揭示涉及ET（A）和/或ET（B）受体激活的ET依赖性效应。在清醒犬中，ET（A）受体阻断剂（冠状动脉内注射Ro-61-1790）使左旋冠状动脉外径（CD）（超声测量法）从3.04±0.12毫米增加了0.10±0.01（P<0.01），而冠状动脉血流量（多普勒法）未改变。同样，在用冠状动脉内注射N（ω）-硝基-L-精氨酸甲酯（L-NAME）阻断NO生成后给予Ro-61-1790时，CD增加（从2.91±0.14毫米增加0.09±0.01；P<0.01）。相比之下，ET（B）受体阻断剂（冠状动脉内注射Ro-46-8443）在有或无L-NAME的情况下均不影响基线CD。在体外，ET（A）受体阻断而非ET（B）受体阻断可降低动脉环中由N（ω）-硝基-L-精氨酸（L-NNA）或前列腺素F2α（PGF2α）引起的张力增加。ET（A）受体阻断也降低了L-NNA在人冠状动脉环中引起的确张力增加。因此，在体内犬心外膜冠状动脉中，ET依赖性收缩是由ET（A）受体而非ET（B）受体介导的。ET依赖性效应在体外和体内均与NO生成水平无关。在人心外膜冠状动脉环中，ET（A）受体阻断也会引起显著舒张。
