Sada T, Koike H, Ikeda M, Sato K, Ozaki H, Karaki H
Cardiovascular Division, Sankyo Co., Ltd., Tokyo, Japan.
Hypertension. 1990 Sep;16(3):245-51. doi: 10.1161/01.hyp.16.3.245.
Cytosolic free calcium concentration ([Ca2+]i) and muscle tension were simultaneously measured in aortic tissue isolated from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats, and SHR chronically treated with a novel angiotensin converting enzyme inhibitor, CS-622. In the presence of 2.5 mM Ca2+ in the bathing solution, aortic [Ca2+]i measured with fura-2 was higher in SHR than in WKY rats, and it was almost the same in CS-622-treated SHR and untreated WKY rats. Increase of external Ca2+ concentration from zero to 2.5 mM elicited a contraction in SHR aortas but not in aortas from both CS-622-treated SHR and untreated WKY rats. When the aortas were contracted by 60 mM K+, however, [Ca2+]i as well as developed tension was similar in the three groups. CGP-28392 (10(-6) M), a Ca2+ channel activator, induced a rhythmic activity superimposed on a gradual increase of [Ca2+]i and tension in SHR aortas but not in the aortas of CS-622-treated SHR or untreated WKY rats. Nicardipine (10(-7) M) decreased the resting [Ca2+]i and the resting tone in SHR aortas, but not in WKY rat aortas. These results suggest that SHR aortas have a higher myogenic tone due to increased [Ca2+]i than WKY rat aortas and that the increased [Ca2+]i is attributed to alterations of dihydropyridine-sensitive Ca2+ channels in SHR aortas. Further, the decrease of the vascular tone induced by long-term administration of the angiotensin converting enzyme inhibitor may be due to a reduction of increased [Ca2+]i in SHR.
在从自发性高血压大鼠（SHR）、血压正常的Wistar-Kyoto（WKY）大鼠以及长期用新型血管紧张素转换酶抑制剂CS-622治疗的SHR分离出的主动脉组织中，同时测量了胞质游离钙浓度（[Ca2+]i）和肌肉张力。在浴液中存在2.5 mM Ca2+的情况下，用fura-2测量的SHR主动脉中的[Ca2+]i高于WKY大鼠，并且在经CS-622治疗的SHR和未治疗的WKY大鼠中几乎相同。外部Ca2+浓度从零增加到2.5 mM会引起SHR主动脉收缩，但不会引起经CS-622治疗的SHR和未治疗的WKY大鼠的主动脉收缩。然而，当主动脉通过60 mM K+收缩时，三组中的[Ca2+]i以及产生的张力相似。Ca2+通道激活剂CGP-28392（10(-6) M）在SHR主动脉中诱导出一种有节律的活动，叠加在[Ca2+]i和张力的逐渐增加上，但在经CS-622治疗的SHR或未治疗的WKY大鼠的主动脉中则不会。尼卡地平（10(-7) M）降低了SHR主动脉中的静息[Ca2+]i和静息张力，但在WKY大鼠主动脉中则没有。这些结果表明，由于[Ca2+]i增加，SHR主动脉比WKY大鼠主动脉具有更高的肌源性张力，并且增加的[Ca2+]i归因于SHR主动脉中二氢吡啶敏感Ca2+通道的改变。此外，长期施用血管紧张素转换酶抑制剂引起的血管张力降低可能是由于SHR中增加的[Ca2+]i减少所致。
