The renal response to diltiazem and nifedipine: comparison with nitroprusside.
We undertook a systematic comparison of the effects of diltiazem and nifedipine and a nonspecific vasodilator, sodium nitroprusside, on renal perfusion, function, and activation of potentially relevant neurohormonal systems in the anesthetized dog. These agents were employed to reduce blood pressure to two levels, a mean arterial pressure level of 100-110 mm Hg, and a subtherapeutic level of 75-85 mm Hg. Renal plasma flow (ERPF) and glomerular filtration rate (GFR) were estimated as the clearances of p-aminohippurate and inulin, respectively. All studies with vasodilators were compared with a group which received placebo over an identical time period. The agents differed both in their action on the renal blood supply and in their activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. ERPF was better maintained at both blood pressure levels with nitroprusside than with either diltiazem (p less than 0.005) or nifedipine (p less than 0.005). GFR was better maintained with nitroprusside and diltiazem than with nifedipine. The rise in plasma catecholamines and plasma renin activity was greatest with nifedipine, least with nitroprusside, and intermediate with diltiazem. Diltiazem was also associated with substantially less stimulation of aldosterone release than was nifedipine. Diltiazem and nifedipine are known to have greater renal vasodilator action when infused into the renal artery than nitroprusside. The better-sustained renal plasma flow and glomerular filtration rate during systemic administration with the latter may well reflect the role of calcium in renal autoregulation and the angiotensin-renin feedback loop. Despite an apparent shared mechanism of action, the calcium-entry-blocking agents differ sufficiently that therapeutic implications are possible.
J L
JL
Blackshear
C
C
Orlandi
G H
GH
Williams
N K
NK
Hollenberg
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005292:Ferricyanides / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D001552:Benzazepines; D005292:Ferricyanides; D009599:Nitroprusside; D004110:Diltiazem; D009543:Nifedipine