McCarron D A, Lucas P A, Shneidman R J, LaCour B, Drüeke T
J Clin Invest. 1985 Sep;76(3):1147-54. doi: 10.1172/JCI112070.
The blood pressure of the spontaneously hypertensive rat (SHR) is influenced by the Ca2+ content of its diet. As the SHR's greater dependence on dietary calcium may reflect a defect in intestinal calcium absorption, we measured in vitro unidirectional Ca2+ flux (J) in the duodenum-jejunum (four segments each) of the SHR (n = 6) and the normotensive Wistar-Kyoto rat (WKY; n = 6) by a modified Ussing apparatus. Because of the known and postulated interactions between Ca2+ and Na+ in both intestinal and vascular tissue, we assessed in vivo the influence of a concurrent manipulation of Na+ intake (three levels: 0.25%, 0.45%, and 1.0%) on the blood pressure development of SHRs (n = 35) and WKYs (n = 35), between 6 and 20 wk of age, exposed to three levels of dietary calcium (0.1, 1.0, and 2%). Net calcium flux (Jnet) (mean +/- SEM) was significantly (P less than 0.01) lower in the SHR (-2.8 +/- 6.3 nmol/cm2 X h) than in the WKY (34.6 +/- 8.8 nmol/cm2 X h). The SHR's decreased Jnet resulted from a significantly (P less than 0.03) lower mucosa-to-serosa flux (Jm-s) in the SHR (41.0 +/- 5.6 nmol/cm2 X h) compared with the Jm-s of the WKY (70.1 +/- 9.1 nmol/cm2 X h). Serosa-to-mucosa flux for calcium did not differ between the SHR (43.8 +/- 6.6 nmol/cm2 X h) and the WKY (35.5 +/- 8.0 nmol/cm2 X h). The SHR's decreased (P less than 0.002) Jm-s was confirmed by additional measurements in SHRs and WKYs. Jm-s was 36.2 +/- 3.7 nmol/cm2 X h in the SHRs (n = 11) and 64.4 +/- 6.7 nmol/cm2 X h in the WKYs (n = 9). The provision of an increased dietary Ca2+ (2% by weight) and increased Na+ (1%) to the SHR prevented the emergence of hypertension (P less than 0.001) (mean +/- SEM systolic blood pressure at 20 wk of age; 135 +/- 5 mmHg for the 2% Ca2+, 1% Na+ SHR vs. 164 +/- 2 mmHg for the control diet SHR). Ca2+ (0.1%) and Na+ (0.25%) restriction accelerated the SHR's hypertension (192 +/- 2 mmHg) (P less than 0.001) and was associated with higher pressures in the WKY (146 +/- 4 mmHg in the restricted WKY vs. 134 +/- 4 mmHg in the control WKY). In a parallel group of 24 SHRs and 24 WKYs fed one of three diets (2% Ca2+/1% Na+; 1% Ca2+/0.45% Na+; or 0.1% Ca2+/0.25% Na+), the heart (P < 0.05) and kidney (P = 0.08) weight of the SHRs varied depending on the diet at 20 wk of age. Low Ca2+ and Na+ intake was associated with increased heart weight (1.6+/-0.9 g) compared with the normal diet for SHR (1.51+/-0.07 g). Increased Ca2+ and Na+ intake was associated with a significantly (P = 0.05) lower heart weight in the SHR (1.37+/-0.03 g) and in the WKY (1.35+/-0.06 g) compared with their normal diet controls. These findings show one mechanism for the SHR's depressor response to supplemental dietary Ca2+ and, in part, explain the sodium dependence of calcium's cardiovascular protective effect.
自发性高血压大鼠（SHR）的血压受其饮食中钙含量的影响。由于SHR对膳食钙的更大依赖性可能反映出肠道钙吸收存在缺陷，我们使用改良的Ussing装置测量了SHR（n = 6）和血压正常的Wistar - Kyoto大鼠（WKY；n = 6）十二指肠 - 空肠（各四段）的体外单向钙通量（J）。由于已知且推测钙与钠在肠道和血管组织中存在相互作用，我们在体内评估了同时改变钠摄入量（三个水平：0.25%、0.45%和1.0%）对6至20周龄的SHR（n = 35）和WKY（n = 35）血压发展的影响，这些大鼠分别摄入三种水平的膳食钙（0.1%、1.0%和2%）。SHR的净钙通量（Jnet）（均值±标准误）显著（P < 0.01）低于WKY，SHR为（-2.8±6.3 nmol/cm²·h），WKY为（34.6±8.8 nmol/cm²·h）。SHR的Jnet降低是由于其黏膜到浆膜的通量（Jm - s）显著（P < 0.03）低于WKY，SHR的Jm - s为（41.0±5.6 nmol/cm²·h），而WKY的Jm - s为（70.1±9.1 nmol/cm²·h）。SHR和WKY之间钙的浆膜到黏膜通量没有差异，SHR为（43.8±6.6 nmol/cm²·h），WKY为（35.5±8.0 nmol/cm²·h）。在SHR和WKY中进行的额外测量证实了SHR的Jm - s降低（P < 0.002）。SHR（n = 11）的Jm - s为36.2±3.7 nmol/cm²·h，WKY（n = 9）的Jm - s为64.4±6.7 nmol/cm²·h。给SHR提供增加的膳食钙（2%重量）和增加的钠（1%）可预防高血压的出现（P < 0.001）（20周龄时的均值±标准误收缩压；2%钙、1%钠的SHR为135±5 mmHg，而对照饮食的SHR为164±2 mmHg）。钙（0.1%）和钠（0.25%）限制加速了SHR的高血压（192±2 mmHg）（P < 0.001），并且与WKY的血压升高有关（限制饮食的WKY为146±4 mmHg，对照WKY为134±4 mmHg）。在一组平行的24只SHR和24只WKY中，喂食三种饮食之一（2%钙/1%钠；1%钙/0.45%钠；或0.1%钙/0.25%钠），20周龄时SHR的心脏（P < 0.05）和肾脏（P = 0.08）重量因饮食而异。与SHR的正常饮食（1.51±0.07 g）相比，低钙和低钠摄入与心脏重量增加（1.6±0.9 g）有关。与它们的正常饮食对照组相比，增加钙和钠的摄入与SHR（1.37±0.03 g）和WKY（1.35±0.06 g）的心脏重量显著（P = 0.05）降低有关。这些发现揭示了SHR对补充膳食钙产生降压反应的一种机制，并部分解释了钙的心血管保护作用对钠的依赖性。
