Oshima T, Young E W, McCarron D A
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland 97201.
Hypertension. 1991 Jul;18(1):111-5. doi: 10.1161/01.hyp.18.1.111.
We have reported that the basal and stimulated cytosolic free calcium concentrations [( Ca2+]i) are elevated in platelets isolated from 12-14-week-old spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto (WKY) rats. To determine whether altered cell calcium metabolism precedes the development of overt hypertension, we measured [Ca2+]i under resting and stimulated conditions in blood platelets and thymic lymphocytes isolated from 4-week-old prehypertensive SHR and WKY rats. Blood pressure was similar in both groups (SHR 95 +/- 8 versus WKY rats 92 +/- 7 mm Hg). Basal [Ca2+]i in platelets was higher in SHR than WKY rats (63.4 +/- 3.9 versus 54.8 +/- 3.1 nM, p less than 0.003). Also the [Ca2+]i response to thrombin was greater in SHR than WKY rats in both the presence and absence of extracellular calcium. For lymphocytes, although no difference was detected in basal [Ca2+]i, the concanavalin A-induced peak [Ca2+]i was higher for SHR than WKY rats in both calcium-containing and calcium-free media. These results suggest that agonist-stimulated calcium influx and calcium discharge from intracellular stores are enhanced in both platelets and lymphocytes of 4-week-old SHR. We conclude that abnormalities in calcium metabolism in two different cell types precede the development of overt hypertension in the SHR.
我们曾报道,与正常血压的Wistar-Kyoto(WKY)大鼠相比,从12至14周龄自发性高血压大鼠(SHR)分离的血小板中,基础和刺激状态下的胞质游离钙浓度[Ca2+]i升高。为了确定细胞钙代谢改变是否先于明显高血压的发生,我们在静息和刺激条件下,测量了从4周龄高血压前期SHR和WKY大鼠分离的血小板和胸腺淋巴细胞中的[Ca2+]i。两组血压相似(SHR为95±8,WKY大鼠为92±7 mmHg)。SHR血小板中的基础[Ca2+]i高于WKY大鼠(63.4±3.9对54.8±3.1 nM,p<0.003)。在存在和不存在细胞外钙的情况下,SHR对凝血酶的[Ca2+]i反应也大于WKY大鼠。对于淋巴细胞,尽管基础[Ca2+]i未检测到差异,但在含钙和无钙培养基中,SHR的伴刀豆球蛋白A诱导的峰值[Ca2+]i均高于WKY大鼠。这些结果表明,4周龄SHR的血小板和淋巴细胞中,激动剂刺激的钙内流和从细胞内储存释放的钙均增强。我们得出结论,两种不同细胞类型的钙代谢异常先于SHR明显高血压的发生。