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Kidney Blood Press Res. 2001;24(1):64-70.
Renal hemodynamic effects of captopril and doxazosin during slight physical activity in hypertensive patients with type-1 diabetes mellitus.

Svarstad E, Gerdts E, Omvik P, Ofstad J, Iversen BM.

Renal Research Group, Institute of Medicine, University of Bergen, Norway. einar.svarstad med.uib.no

Angiotensin-converting enzyme inhibitors are renoprotective in diabetes mellitus through their intrarenal hemodynamic effects. Alpha-1 blockade has variable pre- and postglomerular vasodilatory effects dependent upon the stimulation of the sympathetic nervous system. We tested the hypothesis that the two different classes of drugs have similar renal hemodynamic effects when the patients are examined in an upright position where the sympathetic nervous system is activated. Mean blood pressure (MAP), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were examined in 28 hypertensive type-1 diabetic patients with variable degree of nephropathy treated for a mean period of 7.6 +/- 0.4 months with captopril (n = 13) or doxazosin (n = 15). Average treatment doses were 112 +/- 7 mg/day in the captopril group and 8 +/- 1 mg/day in the doxazosin group. Sitting MAP decreased from 118 +/- 3 to 106 +/- 4 mm Hg after captopril (p < 0.05), and from 117 +/- 4 to 110 +/- 3 mm Hg after doxazosin (p = 0.07). GFR and ERPF were unchanged in both groups. The filtration fraction (FF) decreased from 0.27 +/- 0.02 to 0.25 +/- 0.02 after captopril (p < 0.05) and from 0.26 +/- 0.01 to 0.25 +/- 0.01 after doxazosin (p = 0.08). Calculation of 95% confidence intervals of the difference between the post-treatment values as well as the difference between pre- and post-treatment values of MAP, GFR, ERPF and FF of the two drugs indicates no difference in renal hemodynamic response between the drugs. In conclusion, captopril and doxazosin have similar renal hemodynamic responses when the patients are examined in a situation where the sympathetic nervous system is stimulated, and this suggests that doxazosin has a renoprotective effect beyond the blood pressure-lowering effect.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11174009&dopt=Abstract

J Urol. 2001 Feb;165(2):616-20.
Captopril restores transforming growth factor-beta type II receptor and sensitivity to transforming growth factor-beta in murine renal cell cancer cells.

Miyajima A, Asano T, Hayakawa M.

Department of Urology, National Defense Medical College, Saitama, Japan.

PURPOSE: Captopril is known to inhibit the growth of renal cancer but the mechanism involved has been unclear. The current study elucidates the mechanism of captopril induced inhibition of the growth of the Renca mouse renal cancer cell line involving transforming growth factor-beta, which is known to be a growth inhibitory cytokine in epithelial cells and tissues. MATERIALS AND METHODS: Transforming growth factor-beta in conditioned medium was measured by bioassay. Levels of transforming growth factor-beta and transforming growth factor-beta type II receptor expression messenger RNA were determined by reverse transcriptase-polymerase chain reaction and flow cytometry. Cell viability was determined by bromodeoxyuridine (BrdU) incorporation and tetrazolium bromide assay. RESULTS: Captopril (0.01 to 1 mM.) showed no significant effect on transforming growth factor-beta synthesis or transforming growth factor-beta messenger RNA in Renca cells. On the other hand, 1 mM. captopril significantly inhibited Renca cell growth. Reverse transcriptase-polymerase chain reaction and flow cytometry showed that 1 mM. captopril up-regulated type II receptor expression. CONCLUSIONS: These findings suggest that captopril restores transforming growth factor-beta type II receptor expression and inhibits the growth of Renca cells by increasing their sensitivity to transforming growth factor-beta.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11176447&dopt=Abstract

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