Influence of the endothelium on Ca2+dependency of angiotensin II‐induced contractions of rat aortic rings

Summary—Endothelium‐dependent relaxation has been demonstrated to be involved in the regulation of vascular tone and extracellular Ca2+was found to play a prominent role in this process. Since the dependency on extracellular Ca2+appeared to differ considerably within the arterial tree, possibly as a consequence of vessel‐related endothelium‐dependent mechanisms, we investigated the effects of different compounds affecting Ca2+entry (nifedipine, CoCl2) on angiotensin II‐induced contractions of rat aortic rings with and without endothelium as well as the responses in a Ca2+–“free” solution. For this purpose, rat aortic rings were either undone from their endothelial layer by gentle mechanical rubbing or care was taken to keep the intima intact in case rings where endothelium were required. The presence of an intact endothelium was confirmed by acetylcholine‐induced relaxation. A stronger responsiveness towards angiotensin I, both after a complete concentration‐response curve and after a single maximal concentration of angiotensin II was observed in arterial segments without endothelium. The maximal contraction to a single concentration of angiotensin II (0.1 μM) in the rings without endothelium amounted to 75.8 ± 3.8% of the preceding response to a supramaximal concentration of noradrenaline (= Emax). In rings without the endothelial layer, the contraction was 34.8 ± 3.7% of Emax. This indicates an endothelium‐induced relaxation in aortic rings with endothelium. After incubation with the Ca2+entry blocker nifedipine (1 μM) both rings with and without endothelium were inhibited to the same extent, contractions amounted to 30.7 ± 1.8% and 19.6 ± 1.3% of Emax, respectively. However, incubation in a Ca2+‐“free” medium for 5 min resulted in similar contractions for rings without endothelium (16.4 ± 1.4% of Emax) as for rings with endothelium (15.0 ± 1.6% of Emax). Moreover, CoCl2in a concentration of 300 μM hardly inhibited the contraction of rings with an intact endothelium, a contractile response of 30.5 ± 2.8% of Emaxwas observed. The results of the study suggest that the influx of Ca2+ions is indeed responsible for the endothelium‐mediated relaxation. However, this influx, which cannot be antagonized by nifedipine, but has shown to be affected by CoCl2, suggests that channels intensitive to organic Ca2+entry blockers may be involved.