Do different antihypertensive drugs (enalapril, nifedipine, verapamil, doxazosin) affect renal blood flow autoregulation and glomerular capillary pressure differently in spontaneously hypertensive rats?
In spontaneously hypertensive rats, calcium channel antagonists abolish renal blood flow autoregulation and increase glomerular capillary pressure, whereas ACE inhibitors lower it, suggesting nifedipine monotherapy without strict blood pressure control may accelerate glomerulosclerosis.
The relationship between systemic blood pressure and glomerular capillary pressure (Pgc) in spontaneously hypertensive rats (SHR) during treatment with antihypertensive drugs is still unclear. The effects of an angiotensin-converting enzyme inhibitor (enalapril), two calcium channel antagonists (nifedipine and verapamil), and an alpha1-receptor blocker (doxazosin) on renal blood flow (RBF) autoregulation, Pgc, and renal segmental resistances were therefore studied in SHR. Recordings of RBF autoregulation were done before and 30 min after intravenous infusion of the different drugs, and Pgc was thereafter measured with the stop-flow technique. When the mean arterial pressure (MAP) was reduced to approximately 120 mmHg by infusions of doxazosin or enalapril, the lower pressure limit of RBF autoregulation was reduced significantly. Nifedipine or verapamil abolished RBF autoregulation. Doxazosin did not change Pgc (43.6 +/- 1.4 vs. 46.7 +/- 1.5 mmHg in controls, P > 0.5), enalapril lowered (41.3 +/- 0.8 mmHg, P 0.2 vs. control), whereas Pgc after enalapril was 38.5 +/- 0.5 mmHg (P < 0.05 vs. control). Enalapril reduced Pgc mainly by reducing efferent resistance. During treatment with calcium channel antagonists, Pgc became strictly dependent on MAP. Monotherapy with nifedipine may increase Pgc and by this mechanism accelerate glomerulosclerosis if a strict blood pressure control is not obtained.
Kvam et al. (Thu,) studied this question.