Effects of antihypertensive drugs on autoregulation of RBF and glomerular capillary pressure in SHR.
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 < 0.01), and the calcium channel antagonists increased Pgc [53.7 +/- 1.4 mmHg (nifedipine) and 54.8 +/- 1.2 mmHg (verapamil), P < 0.01]. When MAP was reduced to approximately 85 mmHg by drugs, Pgc was reduced to 43.3 +/- 1.7 mmHg after nifedipine (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.
Renal Research Group, Medical Department A, University of Bergen, N-5021 Bergen, Norway.
F I
FI
Kvam
J
J
Ofstad
B M
BM
Iversen
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology*; D017292:Doxazosin / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004656:Enalapril; D014700:Verapamil; D009543:Nifedipine; D017292:Doxazosin