Autoregulation of total and zonal glomerular filtration rate in spontaneously hypertensive rats during antihypertensive therapy.
The effects of angiotensin II type 1 receptor antagonist (losartan), angiotensin 1-converting enzyme (ACE) inhibitor (enalapril), and calcium channel blocker (nifedipine) on autoregulation of total and zonal glomerular filtration rate (GFR) were studied in spontaneously hypertensive rats (SHRs), 10 and 40 weeks of age, and 10-week-old Wistar-Kyoto (WKY) rats. Untreated animals in each group served as controls. Renal blood flow (RBF) was measured by a transit-time flow probe (Transonic) on the left renal artery. Total and zonal GFR (outer, middle, and inner cortex) were estimated from tubular uptake of 125iodine-labeled aprotinin (125IAp) injected i.v. at control renal arterial pressure (RAP), and 131IAp injected at a RAP reduced to the lower limit of RBF autoregulation. Autoregulation of RBF was reset to higher pressure levels in untreated hypertensive rats. Enalapril normalized this resetting in 10-week-old SHRs, but not in aged SHRs 40 weeks. Losartan did not completely normalize this resetting in either 10-or 40-week-old SHRs, whereas nifedipine impaired RBF autoregulation in both WKYs and SHRs. A decreased autoregulatory compensation of GFR after pressure reduction was observed in losartan-treated 10-week-old SHRs and after all drug regimens in 40-week SHRs. GFR autoregulation in outer, middle, and inner cortex was impaired in losartan-treated 10-and 40-week-old SHRs. With all treatments, the autoregulation in 10- and 40-week-old SHRs was better preserved in the inner than in the outer cortex. The impaired autoregulation may indicate that a part of the dilatory capacity of preglomerular vessels has already been taken out by hypotensive treatment. Renal vascular abnormalities may have an additional effect.
Wang
X
X
Medical Department A, Haukeland Hospital, Bergen, Norway.
Aukland
K
K
Iversen
B M
BM
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004656:Enalapril / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D009543:Nifedipine; D019808:Losartan