The Effect of SQ 14,225 on Systolic Blood Pressure and Urinary Excretion of Vasopressin in the Developing Spontaneously Hypertensive Rat

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SUMMARY In order to assess the relationship in the spontaneously hypertensive (SH) rat between the development of hypertension and the increased secretion of vasopressin which we have shown in this model, SH rats were treated with the orally effective converting enzyme inhibitor, SQ 14,225 (15 to 30 mg/kg-day in the drinking water), from ages 33 to 61 days. Systolic blood pressure (SBP) in the treated rats increased from a pretreatment level of 112 ± 6 (SE) mm Hg to only 136 ± 2 mm Hg by the fourth week of treatment. In the untreated SH rats SBP rose from 116 ± 5 mm Hg to 174 ± 4 mm Hg in this same period. Within 2 days of initiating treatment with SQ 14,225, 24-hour urinary excretion of ADH (UADHV) fell 46% and remained depressed for the duration of treatment, while in the untreated rats UADH V tended to increase. Treatment with SQ 14,225 gradually increased water intake to a level 64% higher than in the untreated rats at the end of 4 weeks. However, the fall in UADHV appeared to precede the increase in water intake. The changes in UADHV and water intake were reflected by an increased urine volume and decreased urine osmolality. All changes were reversed within 9 days after discontinuing treatment with SQ 14,225. The decreased release of vasopressin, suggested by the decreased UADHV, could have been a factor in preventing the development of hypertension in the treated rats to the extent that vasopressin acts as a pressor agent in the SH rat and that blood volume was reduced as a result of the increased urine volume.

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