Yagil Y, Yagil C
Department of Nephrology and Hypertension, Faculty of Health Sciences, Ben-Gurion University, Ashkelon, Israel.
J Hypertens. 1998 Oct;16(10):1481-4. doi: 10.1097/00004872-199816100-00012.
Since the Sabra experimental model of hypertension was developed, it has been known as a model of salt-susceptible hypertension. Because the hypertensive response of the Sabra hypertension-prone strain (SBH/y) is classically elicited by salt loading with a combination of deoxycorticosterone acetate (DOCA) and salt, doubt has now been cast on whether the hypertensive response is due to sensitivity to salt or to mineralocorticoids. The present study was designed to resolve this question.
We studied the blood pressure response of SBH/y to various modes of salt loading. Animals were salt-loaded by administration of: 1% NaCl in drinking water and subcutaneous implantation of a 25 mg DOCA pellet (DOCA-salt); DOCA alone; 1% NaCl in drinking water alone; or 8% NaCl in chow alone. Blood pressure was determined by the tail-cuff method in awake and undisturbed animals.
Within 4 weeks, the DOCA-salt treatment elicited the full hypertensive response previously reported in the SBH/y strain. Salt loading with 8% NaCl in chow reproduced the full hypertensive response observed with DOCA-salt, except that it occurred only after 7 weeks of treatment. Salt loading with DOCA alone raised blood pressure moderately and to a maximal level within 3 weeks; the magnitude of the blood pressure response was, however, significantly smaller than that observed with DOCA-salt or 8% NaCl in chow. Administration of 1% NaCl in water alone elicited no hypertensive response.
The hypertensive response to salt loading in the Sabra experimental model of hypertension is an expression primarily of salt sensitivity, as it can be fully reproduced with salt alone, but not with DOCA alone. The use of the DOCA-salt mode of salt loading in this model, as opposed to salt loading with 8% salt in chow, is a useful way of accelerating the development of salt-sensitive hypertension in SBH/y, which shortens, and therefore facilitates, phenotyping.
自从开发出Sabra高血压实验模型以来,它就被认为是盐敏感性高血压模型。由于Sabra高血压易感品系(SBH/y)的高血压反应传统上是通过醋酸脱氧皮质酮(DOCA)和盐联合负荷盐来引发的,现在人们对这种高血压反应是由于对盐敏感还是对盐皮质激素敏感产生了疑问。本研究旨在解决这个问题。
我们研究了SBH/y对各种负荷盐模式的血压反应。通过以下方式对动物进行负荷盐:饮用水中给予1% NaCl并皮下植入25 mg DOCA丸剂(DOCA-盐);单独给予DOCA;单独在饮用水中给予1% NaCl;或单独在食物中给予8% NaCl。通过尾套法在清醒且未受干扰的动物中测定血压。
在4周内,DOCA-盐处理引发了先前在SBH/y品系中报道的完全高血压反应。在食物中给予8% NaCl负荷盐重现了DOCA-盐观察到的完全高血压反应,只是它仅在治疗7周后出现。单独给予DOCA负荷盐使血压适度升高并在3周内达到最大水平;然而,血压反应的幅度明显小于DOCA-盐或食物中8% NaCl所观察到的幅度。仅在水中给予1% NaCl未引发高血压反应。
在Sabra高血压实验模型中,对负荷盐的高血压反应主要是盐敏感性的表现,因为仅用盐就能完全重现,但仅用DOCA则不能。与在食物中给予8%盐负荷盐相反,在该模型中使用DOCA-盐负荷盐模式是加速SBH/y中盐敏感性高血压发展的一种有用方法,这缩短了并因此便于进行表型分析。