Renal hemodynamic effects of calcium antagonists in rats with reduced renal mass.
The intrarenal hemodynamic effects of antihypertensive agents vary considerably, and these microcirculatory effects may contribute to long-term structural sequelae in the setting of chronic renal disease. To investigate the consequences of blood pressure reduction with calcium antagonists, 5/6 nephrectomized Munich-Wistar rats underwent baseline determinations of mean arterial pressure, whole kidney function, and single nephron glomerular filtration rate, after which intravenous infusions of verapamil or diltiazem were given in doses that acutely normalized blood pressure; control rats received saline vehicle. During the baseline period, all rats exhibited comparably elevated values for mean arterial pressure and single nephron glomerular filtration rate. During the experimental infusion, control rats exhibited continued single nephron hyperfiltration (84 +/- 8 nl/min) as a result of elevations in both glomerular capillary plasma flow rate (330 +/- 36 nl/min) and glomerular capillary hydraulic pressure (68 +/- 3 mm Hg), whereas the glomerular capillary ultrafiltration coefficient was low [0.050 +/- 0.009 nl/(sec.mm Hg)]. Both verapamil (148 +/- 6 to 103 +/- 3 mm Hg, p less than 0.05) and diltiazem (154 +/- 6 to 102 +/- 2 mm Hg, p less than 0.05) normalized arterial pressure, which did not change in control rats (150 +/- 7 to 142 +/- 8 mm Hg). Single nephron hyperfiltration and hyperperfusion were comparable among groups during the experimental period; compared with baseline values, diltiazem (97 +/- 8 to 71 +/- 7 nl/min, p less than 0.05) but not verapamil (90 +/- 7 to 83 +/- 6 nl/min, p = NS) modestly lowered the single nephron glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
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Renal Division, Brigham and Women's Hospital, Boston, MA 02115.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine