Vascular Biology – Hemodynamics – Hypertension
Kidney International (2000) 57, 2064–2071; doi:10.1046/j.1523-1755.2000.00055.x
Effects of spironolactone on systolic blood pressure in experimental diabetic rats
Yan-Jun Liu, Yuichi Nakagawa, Kazuhiko Toya, Ying Wang, Hirokazu Saegusa, Toshiki Nakanishi and Takehiko Ohzeki
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan
Correspondence: Yan-Jun Liu, Ph.D., Department of Pediatrics, Hamamatsu University School of Medicine, 3600 Handa-Cho, Hamamatsu 431–3192, Japan. E-mail: yjliu@hama-med.ac.jp
Received 4 January 1999; Revised 20 October 1999; Accepted 15 December 1999.
Abstract
Effects of spironolactone on systolic blood pressure in diabetic rats.
Background
Mineralocorticoid hormones, which maintain electrolyte balance and blood pressure, are thought to be associated not only with the expression of renal 11
-hydroxysteroid dehydrogenase type 2 (11-HSD2), but also with that of intracellular mineralocorticoid receptors (MRs). The present study was designed to test whether the mineralocorticoid action of glucocorticoid corticosterone on renal MR is involved in the development of diabetes-associated hypertension by measuring the alterations of renal 11-HSD2.
Method
We measured the mean systolic blood pressure, renal 11-HSD1, and mRNA levels in streptozotocin (STZ)-induced diabetic rats that received spironolactone, insulin, or no treatment, and in nondiabetic controls that received spironolactone.
Results
Four weeks after an injection of STZ, the renal 11-HSD2 and mRNA levels were significantly lower in diabetic rats than in control rats, and the mean systolic blood pressure was 14.8% higher in diabetic rats than in controls. Subcutaneous injections of spironolactone into diabetic rats for three weeks partially reversed the decrease in renal 11-HSD2 activity and gene expression, and prevented the mean systolic blood pressure elevation. Spironolactone treatment for one week also resulted in a significant reduction in mean systolic blood pressure during the development of diabetic hypertension. However, treatment with STZ did not significantly decrease the renal 11-HSD1 activity and mRNA expression, and spironolactone treatment did not exert a significant effect on this enzyme in STZ-induced diabetic rats.
Conclusion
In the development of diabetes-induced hypertension, the effect of spironolactone on mean systolic blood pressure may be associated with the mineralocorticoid effects of corticosterone on renal MR, as well as an alteration of renal 11-HSD2 activity and its mRNA expression in insulin-dependent diabetic rats.
Keywords:
11-hydroxysteroid dehydrogenase, blood pressure, mineralocorticoid receptor, diabetes mellitus, IDDM
