Does the Sabra hypertension-prone rat represent a model of salt or mineralocorticoid sensitivity?

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.