title: Threshold sodium excretory and renal blood flow effects of angiotensin converting enzyme inhibition.
abstract: OBJECTIVE
  To probe the potential influence of a high renal tubular level of angiotensin II on sodium reabsorption using angiotensin converting enzyme inhibitors and a non-peptide angiotensin antagonist.
  
  
  METHODS
  Systemic arterial blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12), ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in graded doses to examine whether the threshold dose that increased RBF was lower than that which increased sodium excretion rate (Na+ excretion rate).
  
  
  RESULTS
  Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4 micrograms/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra-arterially) did not change blood pressure except for a slight effect with the two higher doses. These three agents increased RBF to about the same degree, between 6% and 18%, which was relatively large compared with the maximal vasodilator response achievable in the kidney with acetylcholine (30-37%). Captopril given intra-arterially had a more consistent effect on Na+ excretion rate than either ramiprilat or EXP 3174. An increase in Na+ excretion rate occurred with captopril ranging from 44% to 78%, whereas no significant change was obtained with the other drugs. The dose of captopril that increased RBF was the same as that which increased Na+ excretion rate. In those experiments in which ramiprilat resulted in an increase in Na+ excretion rate (five of 10 experiments), the effective dose was the same as that which increased RBF.
  
  
  CONCLUSIONS
  When administered by the intra-arterial route, captopril was more effective in increasing Na+ excretion rate than either ramiprilat or EXP 3174. Although the threshold dose of captopril and ramiprilat required to increase Na+ excretion rate and RBF was similar, suggesting blockade of a common angiotensin II pool, there was not a good correlation between these two effects.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: E W
authors.initials: EW
authors.lastname: Dunham
authors.forename: B G
authors.initials: BG
authors.lastname: Zimmerman
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004056:Differential Threshold / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009318:Natriuresis / Q000187:drug effects*; D009392:Nephrectomy; D011188:Potassium / Q000652:urine; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C052549:ramiprilat; D002216:Captopril; C066026:losartan carboxylic acid; D019808:Losartan; D017257:Ramipril; D011188:Potassium