Effects of antihypertensive drugs on autoregulation of RBF and glomerular capillary pressure in SHR

The relationship between systemic blood pressure and glomerular capillary pressure (P ) 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 α -receptor blocker (doxazosin) on renal blood flow (RBF) autoregulation, P , 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 P was thereafter measured with the stop-flow technique. When the mean arterial pressure (MAP) was reduced to ∼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 P (43.6 ± 1.4 vs. 46.7 ± 1.5 mmHg in controls, P > 0.5), enalapril lowered (41.3 ± 0.8 mmHg, P < 0.01), and the calcium channel antagonists increased P [53.7 ± 1.4 mmHg (nifedipine) and 54.8 ± 1.2 mmHg (verapamil), P < 0.01]. When MAP was reduced to ∼85 mmHg by drugs, P was reduced to 43.3 ± 1.7 mmHg after nifedipine ( P > 0.2 vs. control), whereas P after enalapril was 38.5 ± 0.5 mmHg ( P < 0.05 vs. control). Enalapril reduced P mainly by reducing efferent resistance. During treatment with calcium channel antagonists, P became strictly dependent on MAP. Monotherapy with nifedipine may increase P and by this mechanism accelerate glomerulosclerosis if a strict blood pressure control is not obtained.