Why the study?
Does SCH 23390 hydrochloride reverse hypertrophic parameters in male Sprague-Dawley rats with abdominal aortic constriction?
Does SCH 23390 hydrochloride reverse hypertrophic parameters in male Sprague-Dawley rats with abdominal aortic constriction?
Upregulation of renal D1 receptors occurs after abdominal aortic constriction, and D1 receptor antagonism may reverse cardiac hypertrophy.
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D1 antagonism merits further preclinical study in hypertrophy; leaves open any role in human cardiac disease.
The characteristics of dopamine (D) receptors were studied in kidney using the radiolabelled receptor assay of [3H]-SCH-23390 for D1 and [3H]-sulpiride for D2 receptors during cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 28 days thereafter. Sham operated animals without aortic constriction were used as control. 2. Membranes obtained from kidney cortex showed an increase in the number of binding sites (Bmax) of D1 receptors in the aortic banded group. The apparent affinity for the ligand (Kd) was unchanged with D1 receptors, as compared to sham control. Both Bmax and Kd were unchanged for D2 receptors in the aortic banded group. 3. Autoradiographic data further reinforced the findings, showing an increased number of D1 receptors in the kidney at 28 days after abdominal aortic constriction. These changes were associated with an increase in plasma renin activity in the aortic banded group. Further, Na(+)-K(+)-ATPase as measured by fmol of 32Pi released from [gamma-32P]-ATP, was decreased in the kidney cortex of banded animals. 4. Reversal of hypertrophic parameters was observed in the aortic banded group treated for 14 days with SCH 23390 hydrochloride (0.1 mg kg-1 i.p.), a known D1 receptor antagonist. 5. The present study shows an upregulation of renal D1 receptors following abdominal aortic constriction and it is suggested that upregulation of D receptors may be involved in the development of cardiac hypertrophy.
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Mukherjee et al. (1994) studied this question.
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