In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 1 ( 1999-01), p. 137-144
Abstract:
Abstract —The ability of endothelin receptor blockade to prevent and to treat established cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist A127722 . SHRSP were subjected to 1% NaCl intake. The start of treatment with A127722 (35 and 70 mg · kg −1 · d −1 , respectively) was either synchronized with salt loading or initiated after the first observation of cerebral edema with T 2 -weighted magnetic resonance imaging. In untreated control animals median survival was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset A127722 treatment increased median survival to 233 days (range, 92 to 407 days; P 〈 0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days; P 〈 0.05 versus control) with 70 mg/kg. The development of cerebral edema was prevented, and systolic blood pressure and proteinuria were dose-dependently reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages in the basal ganglia shortly before death. Late-onset A127722 treatment failed to affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral edema was reduced but not as well as in early-onset treatment. Development of hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722 treatment was initiated at the start of salt-loading. However, A127722 treatment did not prolong survival in SHRSP with cerebral edema. This suggests that in SHRSP the endothelin A receptor participates actively in the development of increased blood pressure and initiation of organ damage but participates minimally in established malignant hypertension and progression of target-organ damage.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.33.1.137
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1999
detail.hit.zdb_id:
2094210-2
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