Source
Institut für Klinische Pharmakologie und Toxikologie, Charité Centrum für Therapieforschung, Germany.
Abstract
AIMS:
In patients with renal disease the cardiovascular risk is greatly increased, and endothelial dysfunction is assumed to play a pivotal role in this process. Therefore we compared treatment effects of a beta-blocker with additional vasodilatory capacities (nebivolol) and a beta-blocker lacking these actions (metoprolol) on intrarenal and coronary vascular function in a rat model of renal failure with hypertension.
MAIN METHODS:
Renal failure was induced by 5/6-nephrectomy (Nx) and analyzed after 4 weeks in Wistar rats. Untreated Nx, Nx/nebivolol 6 mg/d (Nx-Nebi); Nx/metoprolol 60 mg/d (Nx-Meto) and sham-operated (Sham) animals were studied. Isolated small renal and coronary arteries were investigated for endothelium-dependent relaxation to acetylcholine (ACh) and for the contribution of the endothelial mediators NO and endothelium-derived hyperpolarizing factor (EDHF).
KEY FINDINGS:
Systolic blood pressure (SBP) was significantly increased in Nx, Nx-Nebi, and Nx-Meto (168+/-5, 153+/-3, and 162+/-6 mmHg) compared to Sham (138+/-3 mmHg, p<0.05, respectively). The increase in albuminuria of Nx (120-fold vs. Sham, p<0.0001) was almost (-85%) normalized by nebivolol compared to Sham (p<0.05), whereas metoprolol induced no significant effect. Renal arteries showed significantly increased Ach-relaxation in Nx and Nx-Nebi (Emax 86+/-4% and 76+/-7%, p<0.05) due to an increase in EDHF-mediated dilation (Emax_EDHF 78+/-7% and 73+/-6%) compared to Sham (Emax 54+/-4% and Emax_EDHF 44+/-6%) and Nx-Meto (Emax 42+/-12% and Emax_EDHF 18+/-5%). ACh-relaxation in coronary arteries was similar between groups but the contribution of NO (relative to EDHF) was strongly increased by nebivolol.
SIGNIFICANCE:
The present findings offer an explanation of the nephroprotective effect of intrarenal endothelial function in renal failure.