Uninephrectomized rats were administered 10 mg of Metopirone (Su-4885; metyrapone), an adrenal 11β-hydroxylase inhibitor, ip either once or twice daily for 6 weeks. All were given 1% sodium chloride as drinking solution. Both Metopirone-treated groups showed a significant elevation in systolic blood pressure. All rats were sacrificed 24 hr after the last injection of Metopirone. Adrenals were collected and corticosteroidogenesis from progesterone, measured in adrenal homogenates, was not impaired by Metopirone treatment. However, in short-term studies when rats were sacrificed either 1 or 4 hr after the final administration of Metopirone, inhibition of 11β-hydroxylation was demonstrable in vitro. The hypertensive groups did show a substantial increase in plasma 11-deoxycorticosterone (DOC) levels, thus indicating some inhibition of 11β- hydroxylase in vivo. Adrenal hypertrophy in those rats treated twice daily with Metopirone further substantiated the effectiveness of the dose of Metopirone employed in th...
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