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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980;71(2):499–506. doi: 10.1111/j.1476-5381.1980.tb10963.x

A comparison of the ability of two angiotensin II receptor blocking drugs, 1-Sar, 8-Ala angiotensin II and 1-Sar, 8-Ile angiotensin II, to modify the regulation of glomerular filtration rate in the cat

EJ Johns
PMCID: PMC2044463  PMID: 7470759

Abstract

1 Modest stimulation of the renal nerves in the anaesthetized unilaterally nephrectomized cat resulted in a 15% fall in renal blood flow, no change in glomerular filtration rate and significant falls in both the absolute and fractional rates of sodium excretion.

2 The haemodynamic responses to nerve stimulation were not modified by angiotensin II blockade with 1-Sar, 8-Ala angiotensin II although the fall in absolute, but not fractional sodium excretion was significantly larger. In contrast, stimulation of renal nerves following administration of 1-Sar, 8-Ileangiotensin II caused a significant fall in glomerular filtration rate. The reductions in both absolute and fractional sodium were of the same magnitude as in the absence of drug.

3 Both renal blood flow and glomerular filtration rate were autoregulated during the reduction of renal perfusion pressure and this was associated with reductions in both absolute and fractional sodium excretions.

4 In the presence of 1-Sar, 8-Ala angiotensin II, the haemodynamic and sodium excretory responses to reductions in renal perfusion pressure were not significantly different from those recorded in the absence of drug. However, following administration of 1-Sar, 8-Ile angiotensin II, renal blood flow but not glomerular filtration rate, was autoregulated during reduction in renal perfusion pressure. The falls in absolute and fractional sodium excretions caused by this manoeuvre were of similar magnitude to those obtained in the absence of drug.

5 The results obtained using the 1-Sar, 8-Ile angiotensin II are consistent with angiotensin II having an important intra-renal site of action to regulate glomerular filtration rate, possibly via an action at the efferent arteriole. Administration of 1-Sar, 8-Ala angiotensin II was without effect on the regulation of renal haemodynamics which it is suggested reflects a limitation in the use of this particular compound as an intrarenal angiotensin II antagonist.

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Selected References

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  1. Abe Y., Kishimoto T., Yamamoto K. Effect of angiotensin II antagonist infusion on autoregulation of renal blood flow. Am J Physiol. 1976 Oct;231(4):1267–1271. doi: 10.1152/ajplegacy.1976.231.4.1267. [DOI] [PubMed] [Google Scholar]
  2. Anderson G. H., Jr, Streeten D. H., Dalakos T. G. Pressor response to 1-sar-8-ala-angiotensin II (saralasin) in hypertensive subjects. Circ Res. 1977 Mar;40(3):243–250. doi: 10.1161/01.res.40.3.243. [DOI] [PubMed] [Google Scholar]
  3. Anderson R. J., Taher M. S., Cronin R. E., McDonald K. M., Schrier R. W. Effect of beta-adrenergic blockade and inhibitors of angiotensin II and prostaglandins on renal autoregulation. Am J Physiol. 1975 Sep;229(3):731–736. doi: 10.1152/ajplegacy.1975.229.3.731. [DOI] [PubMed] [Google Scholar]
  4. Arendshorst W. J., Finn W. F. Renal hemodynamics in the rat before and during inhibition of angiotensin II. Am J Physiol. 1977 Oct;233(4):F290–F297. doi: 10.1152/ajprenal.1977.233.4.F290. [DOI] [PubMed] [Google Scholar]
  5. BOJESEN E. A method for determination of inulin in plasma and urine. Acta Med Scand Suppl. 1952;266:275–282. doi: 10.1111/j.0954-6820.1952.tb13376.x. [DOI] [PubMed] [Google Scholar]
  6. Colindres R. E., Gottschalk C. W. Neural control of renal tubular sodium reabsorption in the rat: single nephron analysis. Fed Proc. 1978 Apr;37(5):1218–1221. [PubMed] [Google Scholar]
  7. Coote J. H., Johns E. J., Macleod V. H., Singer B. Effect of renal nerve stimulation, renal blood flow and adrenergic blockade on plasma renin activity in the cat. J Physiol. 1972 Oct;226(1):15–36. doi: 10.1113/jphysiol.1972.sp009971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DiBona G. F. Neurogenic regulation of renal tubular sodium reabsorption. Am J Physiol. 1977 Aug;233(2):F73–F81. doi: 10.1152/ajprenal.1977.233.2.F73. [DOI] [PubMed] [Google Scholar]
  9. Freeman R. H., Davis J. O., Vitale S. J., Johnson J. A. Intrarenal role of angiotensin II. Homeostatic regulation of renal blood flow in the dog. Circ Res. 1973 Jun;32(6):692–698. doi: 10.1161/01.res.32.6.692. [DOI] [PubMed] [Google Scholar]
  10. Gagnon J. A., Rice M. K., Flamenbaum W. Effect of angiotensin converting enzyme inhibition on renal autoregulation. Proc Soc Exp Biol Med. 1974 Jun;146(2):414–418. doi: 10.3181/00379727-146-38117. [DOI] [PubMed] [Google Scholar]
  11. Hall J. E., Coleman T. G., Guyton A. C., Balfe J. W., Salgado H. C. Intrarenal role of angiotensin II and [des-Asp1]angiotensin II. Am J Physiol. 1979 Mar;236(3):F252–F259. doi: 10.1152/ajprenal.1979.236.3.F252. [DOI] [PubMed] [Google Scholar]
  12. Hall J. E., Guyton A. C., Cowley A. W., Jr Dissociation of renal blood flow and filtration rate autoregulation by renin depletion. Am J Physiol. 1977 Mar;232(3):F215–F221. doi: 10.1152/ajprenal.1977.232.3.F215. [DOI] [PubMed] [Google Scholar]
  13. Hall J. E., Guyton A. C., Jackson T. E., Coleman T. G., Lohmeier T. E., Trippodo N. C. Control of glomerular filtration rate by renin-angiotensin system. Am J Physiol. 1977 Nov;233(5):F366–F372. doi: 10.1152/ajprenal.1977.233.5.F366. [DOI] [PubMed] [Google Scholar]
  14. Johns E. J. Action of angiotensin I converting enzyme inhibitor on the control of renal function in the cat. Clin Sci (Lond) 1979 Apr;56(4):365–371. doi: 10.1042/cs0560365. [DOI] [PubMed] [Google Scholar]
  15. Johns E. J., Lewis B. A., Singer B. The sodium-retaining effect of renal nerve activity in the cat: role of angiotensin formation. Clin Sci Mol Med. 1976 Jul;51(1):93–102. doi: 10.1042/cs0510093. [DOI] [PubMed] [Google Scholar]
  16. Johns E. J., Singer B. Specificity of blockade of renal renin release by propranolol in the cat. Clin Sci Mol Med. 1974 Oct;47(4):331–343. doi: 10.1042/cs0470331. [DOI] [PubMed] [Google Scholar]
  17. Kaloyanides G. J., Bastron R. D., DiBona G. F. Impaired autoregulation of blood flow and glomerular filtration rate in the isolated dog kidney depleted of renin. Circ Res. 1974 Sep;35(3):400–412. doi: 10.1161/01.res.35.3.400. [DOI] [PubMed] [Google Scholar]
  18. Kaloyanides G. J., DiBona G. F. Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney. Am J Physiol. 1976 Apr;230(4):1078–1083. doi: 10.1152/ajplegacy.1976.230.4.1078. [DOI] [PubMed] [Google Scholar]
  19. Kimbrough H. M., Jr, Vaughan E. D., Jr, Carey R. M., Ayers C. R. Effect of intrarenal angiotensin II blockade on renal function in conscious dogs. Circ Res. 1977 Feb;40(2):174–178. doi: 10.1161/01.res.40.2.174. [DOI] [PubMed] [Google Scholar]
  20. Laragh J. H., Case D. B., Wallace J. M., Keim H. Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade. Fed Proc. 1977 Apr;36(5):1781–1787. [PubMed] [Google Scholar]
  21. Marshall G. R. Structure--activity relations of antagonists of the renin--angiotensin system. Fed Proc. 1976 Nov;35(13):2494–2501. [PubMed] [Google Scholar]
  22. Mimran A., Hinrichs K. J., Hollenberg N. K. Characterization of smooth muscle receptors for angiotensin: studies with an antagonist. Am J Physiol. 1974 Jan;226(1):185–190. doi: 10.1152/ajplegacy.1974.226.1.185. [DOI] [PubMed] [Google Scholar]
  23. Murray R. D., Malvin R. L. Intrarenal renin and autoregulation of renal plasma flow and glomerular filtration rate. Am J Physiol. 1979 Jun;236(6):F559–F566. doi: 10.1152/ajprenal.1979.236.6.F559. [DOI] [PubMed] [Google Scholar]
  24. Pals D. T., Masucci F. D., Denning G. S., Jr, Sipos F., Fessler D. C. Role of the pressor action of angiotensin II in experimental hypertension. Circ Res. 1971 Dec;29(6):673–681. doi: 10.1161/01.res.29.6.673. [DOI] [PubMed] [Google Scholar]
  25. Rubin B., Antonaccio M. J., Horovitz Z. P. Captopril (SQ 14,225) (D-3-mercapto-2-methylpropranoyl-L-proline): a novel orally active inhibitor of angiotensin-converting enzyme and antihypertensive agent. Prog Cardiovasc Dis. 1978 Nov-Dec;21(3):183–194. doi: 10.1016/0033-0620(78)90024-5. [DOI] [PubMed] [Google Scholar]
  26. SELKURT E. E. Effect of pulse pressure and mean arterial pressure modification on renal hemodynamics and electrolyte and water excretion. Circulation. 1951 Oct;4(4):541–551. doi: 10.1161/01.cir.4.4.541. [DOI] [PubMed] [Google Scholar]
  27. Wallace J. M., Case D. B., Laragh J. H., Keim H. J., Drayer J. I., Sealey J. E. The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy. Circ Res. 1979 Jan;44(1):38–44. doi: 10.1161/01.res.44.1.38. [DOI] [PubMed] [Google Scholar]
  28. Zambraski E. J., DiBona G. F. Angiotensin II in antinatriuresis of low-level renal nerve stimulation. Am J Physiol. 1976 Oct;231(4):1105–1110. doi: 10.1152/ajplegacy.1976.231.4.1105. [DOI] [PubMed] [Google Scholar]

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