Touyz R M, Tolloczko B, Schiffrin E L
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
J Hypertens. 1994 Jun;12(6):663-73.
To determine the differential calcium responses to two vasoconstrictor peptides, angiotensin II (Ang II) and endothelin-1, in vascular smooth muscle cells derived from mesenteric arteries from young and adult normotensive and hypertensive rats.
Effects of Ang II and endothelin-1 on cytosolic free calcium concentration in primary cultured unpassaged single vascular smooth muscle cells from mesenteric arteries of Wistar-Kyoto (WKY), Wistar and spontaneously hypertensive rats (SHR) aged 3, 9 and 17 weeks were examined microphotometrically using fura-2 methodology.
Basal cytosolic free calcium concentration was significantly increased in cells from SHR aged 9 and 17 weeks compared with cells from age-matched WKY and Wistar rats. Ang II and endothelin-1 significantly increased cell cytosolic free calcium in all rat groups at all ages. Responses to low concentrations of Ang II (1 nmol/l) were significantly higher in cells from SHR aged 9 and 17 weeks than in age-matched controls. This was confirmed in cells from rats aged 17 weeks with full concentration-response curves, which also showed that the pD2 for Ang II for WKY rats was significantly different from that of SHR. In cells from SHR at all ages Ang II-stimulated cytosolic free calcium remained persistently high, whereas in cells from WKY and Wistar rats basal levels were reached within 100 s after the maximal response. Low concentrations of endothelin-1 elicited significantly lower cytosolic free calcium responses in cells from SHR aged 17 weeks compared with age-matched controls. The time course of cytosolic free calcium responses to endothelin-1 were similar in the groups.
In primary cultured unpassaged mesenteric vascular smooth muscle cells from adult SHR, cytosolic free calcium concentration responses to Ang II are enhanced, whereas responses to low concentrations of endothelin-1 are slightly reduced. The differential effects of these two vasoconstrictor peptides may contribute to their relative roles in modulating vascular smooth muscle cell cytosolic free calcium in SHR.
确定来自年轻和成年正常血压及高血压大鼠肠系膜动脉的血管平滑肌细胞对两种血管收缩肽——血管紧张素II(Ang II)和内皮素-1的钙反应差异。
采用fura-2方法,通过显微光度法检测Ang II和内皮素-1对3、9和17周龄的Wistar-Kyoto(WKY)大鼠、Wistar大鼠和自发性高血压大鼠(SHR)肠系膜动脉原代培养未传代的单个血管平滑肌细胞胞质游离钙浓度的影响。
与年龄匹配的WKY和Wistar大鼠的细胞相比,9周龄和17周龄SHR的细胞基础胞质游离钙浓度显著升高。在所有年龄组的所有大鼠中,Ang II和内皮素-1均显著增加细胞胞质游离钙。9周龄和17周龄SHR的细胞对低浓度Ang II(1 nmol/l)的反应显著高于年龄匹配的对照组。这在17周龄大鼠的细胞中通过完整的浓度-反应曲线得到证实,该曲线还表明WKY大鼠对Ang II的pD2与SHR的显著不同。在所有年龄的SHR细胞中,Ang II刺激的胞质游离钙持续保持在高水平,而在WKY和Wistar大鼠的细胞中,最大反应后100秒内达到基础水平。与年龄匹配的对照组相比,17周龄SHR的细胞对低浓度内皮素-1引起的胞质游离钙反应显著降低。各实验组对内皮素-1的胞质游离钙反应的时间进程相似。
在成年SHR原代培养未传代的肠系膜血管平滑肌细胞中,对Ang II的胞质游离钙浓度反应增强,而对低浓度内皮素-1的反应略有降低。这两种血管收缩肽的不同作用可能有助于它们在调节SHR血管平滑肌细胞胞质游离钙方面的相对作用。