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. 1974 Dec;54(6):1413–1419. doi: 10.1172/JCI107888

Comparison of the Effects on Renin Release of Beta Adrenergic Antagonists with Differing Properties

Michael A Weber 1, Gordon S Stokes 1, Judith M Gain 1
PMCID: PMC301696  PMID: 4154950

Abstract

Continuous 6-h infusions of the beta adrenergic blockers d,l-propranolol or oxprenolol significantly reduced plasma renin activity (PRA) and mean blood pressure in the resting rabbit and prevented the stimulatory effects of isoproterenol on renin release and heart rate. These actions were due to blockade of beta receptors, for the inactive isomer, d-propranolol, had no effect. Despite sustained high plasma concentrations of d,l-propranolol (0.2 μg/ml) in the unstimulated animal, PRA did not fall below 36% of control values, suggesting that basal renin secretion is maintained partly by factors other than beta adrenergic mechanisms.

Prindolol, another beta blocker, also abolished the effects of isoproterenol on renin and on the heart, and reduced blood pressure in the resting animal. However, prindolol increased resting PRA and heart rate, and in animals already receiving d,l-propranolol, it raised PRA and heart rate without further altering blood pressure. This suggests that the effect on PRA of prindolol was due to its intrinsic sympathomimetic activity and not hypotension-mediated mechanisms. The observation that the blood pressure-lowering effect of prindolol was associated with a rise in PRA, while another beta antagonist, H 35/25, lowered PRA but had no effect on blood pressure, indicates that the hypotensive action of beta blockers is unrelated to their effects on renin release.

In both unstimulated and isoproterenol-challenged animals, only blockers possessing beta-1 receptor affinity (d,l-propranolol, oxprenolol, prindolol, practolol, and metoprolol) affected heart rate, while effects on PRA were more prominent with agents possessing beta-2 activity (d,l-propranolol, oxprenolol, prindolol, and H 35/25). Thus, the changes in PRA caused by the beta adrenergic blockers appear to be dependent upon the summation of their direct effects, antagonistic or sympathomimetic, on beta-2 adrenergic receptors regulating renin release.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ablad B., Carlsson E., Ek L. Pharmacological studies of two new cardioselective adrenergic beta-receptor antagonists. Life Sci I. 1973 Feb 1;12(3):107–119. doi: 10.1016/0024-3205(73)90368-8. [DOI] [PubMed] [Google Scholar]
  2. Amery A., Billiet L., Fagard R. Letter: Beta receptors and renin release. N Engl J Med. 1974 Jan 31;290(5):284–284. doi: 10.1056/NEJM197401312900516. [DOI] [PubMed] [Google Scholar]
  3. Assaykeen T. A., Clayton P. L., Goldfien A., Ganong W. F. The effect of alpha- and beta-adrenergic blocking agents on the renin response to hypoglycemia and epinephrine in dogs. Endocrinology. 1970 Dec;87(6):1318–1322. doi: 10.1210/endo-87-6-1318. [DOI] [PubMed] [Google Scholar]
  4. Barrett A. M., Carter J. Comparative chronotropic activity of beta-adrenoceptive antagonists. Br J Pharmacol. 1970 Nov;40(3):373–381. doi: 10.1111/j.1476-5381.1970.tb10619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brunner H. R., Kirshman J. D., Sealey J. E., Laragh J. H. Hypertension of renal origin: evidence for two different mechanisms. Science. 1971 Dec 24;174(4016):1344–1346. doi: 10.1126/science.174.4016.1344. [DOI] [PubMed] [Google Scholar]
  6. Bühler F. R., Laragh J. H., Baer L., Vaughan E. D., Jr, Brunner H. R. Propranolol inhibition of renin secretion. A specific approach to diagnosis and treatment of renin-dependent hypertensive diseases. N Engl J Med. 1972 Dec 14;287(24):1209–1214. doi: 10.1056/NEJM197212142872401. [DOI] [PubMed] [Google Scholar]
  7. Bühler F. R., Laragh J. H., Vaughan E. D., Jr, Brunner H. R., Gavras H., Baer L. Antihypertensive action of propranolol. Specific antirenin responses in high and normal renin forms of essential, renal, renovascular and malignant hypertension. Am J Cardiol. 1973 Sep 20;32(4):511–522. doi: 10.1016/s0002-9149(73)80043-8. [DOI] [PubMed] [Google Scholar]
  8. Coltart D. J., Shand D. G. Plasma propranolol levels in the quaniitative assessment of beta-adrenergic blockade in man. Br Med J. 1970 Sep 26;3(5725):731–734. doi: 10.1136/bmj.3.5725.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dollery C. T., Paterson J. W., Conolly M. E. Clinical pharmacology of beta-receptor-blocking drugs. Clin Pharmacol Ther. 1969 Nov-Dec;10(6):765–799. [PubMed] [Google Scholar]
  10. Dunlop D., Shanks R. G. Selective blockade of adrenoceptive beta receptors in the heart. Br J Pharmacol Chemother. 1968 Jan;32(1):201–218. doi: 10.1111/j.1476-5381.1968.tb00444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Esler M. D., Nestel P. J. Evaluation of practolol in hypertension. Effects on sympathetic nervous system and renin responsiveness. Br Heart J. 1973 May;35(5):469–474. doi: 10.1136/hrt.35.5.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fenyvesi T., George C. F., Dollery C. T. Effect of -adrenoceptor antagonists on the decline of the chronotropic response to isoprenaline. J Pharm Pharmacol. 1972 Apr;24(4):313–317. doi: 10.1111/j.2042-7158.1972.tb08991.x. [DOI] [PubMed] [Google Scholar]
  13. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  14. Lands A. M., Arnold A., McAuliff J. P., Luduena F. P., Brown T. G., Jr Differentiation of receptor systems activated by sympathomimetic amines. Nature. 1967 May 6;214(5088):597–598. doi: 10.1038/214597a0. [DOI] [PubMed] [Google Scholar]
  15. Leishman A. W., Thirkettle J. L., Allen B. R., Dixon R. A. Controlled trial of oxprenolol and practolol in hypertension. Br Med J. 1970 Nov 7;4(5731):342–344. doi: 10.1136/bmj.4.5731.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Levy B., Wilkenfeld B. E. Selective interactions with beta adrenergic receptors. Fed Proc. 1970 Jul-Aug;29(4):1362–1364. [PubMed] [Google Scholar]
  17. Michelakis A. M., McAllister R. G. The effect of chronic adrenergic receptor blockade on plasma renin activity in man. J Clin Endocrinol Metab. 1972 Feb;34(2):386–394. doi: 10.1210/jcem-34-2-386. [DOI] [PubMed] [Google Scholar]
  18. Morgan T. O., Louis W. J., Dawborn J. K., Doyle A. E. The use of prindolol (Visken) in the treatment of hypertension. Med J Aust. 1972 Aug 5;2(6):309–312. doi: 10.5694/j.1326-5377.1972.tb47306.x. [DOI] [PubMed] [Google Scholar]
  19. Otsuka K., Assaykeen T. A., Goldfien A., Ganong W. F. Effect of hypoglycemia on plasma renin activity in dogs. Endocrinology. 1970 Dec;87(6):1306–1317. doi: 10.1210/endo-87-6-1306. [DOI] [PubMed] [Google Scholar]
  20. Pacha W. L. A method for the fluorimetric determination of 4-(2-hydroxy-3-isopropylaminopropoxy)-indole (LB46), a beta-blocking agent, in plasma and urine. Experientia. 1969 Aug 15;25(8):802–803. doi: 10.1007/BF01897885. [DOI] [PubMed] [Google Scholar]
  21. Passo S. S., Assaykeen T. A., Goldfien A., Ganong W. F. Effect of alpha- and beta-adrenergic blocking agents on the increase in renin secretion produced by stimulation of the medulla oblongata in dogs. Neuroendocrinology. 1971;7(2):97–104. doi: 10.1159/000121957. [DOI] [PubMed] [Google Scholar]
  22. Pettinger W. A., Campbell W. B., Keeton K. Adrenergic component of renin release induced by vasodilating antihypertensive drugs in the rat. Circ Res. 1973 Jul;33(1):82–86. doi: 10.1161/01.res.33.1.82. [DOI] [PubMed] [Google Scholar]
  23. Porte D., Jr Beta adrenergic stimulation of insulin release in man. Diabetes. 1967 Mar;16(3):150–155. doi: 10.2337/diab.16.3.150. [DOI] [PubMed] [Google Scholar]
  24. Shand D. G., Nuckolls E. M., Oates J. A. Plasma propranolol levels in adults with observations in four children. Clin Pharmacol Ther. 1970 Jan-Feb;11(1):112–120. doi: 10.1002/cpt1970111112. [DOI] [PubMed] [Google Scholar]
  25. Stokes G. S., Goldsmith R. F., Starr L. M., Gentle J. L., Mani M. K., Stewart J. H. Plasma renin activity in human hypertension. Circ Res. 1970 Oct;27(Suppl):207+–207+. [PubMed] [Google Scholar]
  26. Stokes G. S., Weber M. A., Thornell I. R. Beta-blockers and plasma renin activity in hypertension. Br Med J. 1974 Jan 12;1(5897):60–62. doi: 10.1136/bmj.1.5897.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stokes G. S., Weber M. A., Thornell I. R., Stoker L. M. Effects of acute and chronic administration of propranolol on blood pressure and plasma renin activity in hypertensive patients. Prog Biochem Pharmacol. 1974;9:29–44. [PubMed] [Google Scholar]
  28. Tobert J. A., Slater J. D., Fogelman F., Lightman S. L., Kurtz A. B., Payne N. N. The effect in man of (+)-propranolol and racemic propranolol on renin secretion stimulated by orthostatic stress. Clin Sci. 1973 Mar;44(3):291–295. doi: 10.1042/cs0440291. [DOI] [PubMed] [Google Scholar]
  29. Todd E. P., Vick R. L. Kalemotropic effect of epinephrine: analysis with adrenergic agonists and antagonists. Am J Physiol. 1971 Jun;220(6):1964–1969. doi: 10.1152/ajplegacy.1971.220.6.1964. [DOI] [PubMed] [Google Scholar]
  30. Vander A. J. Direct effects of potassium on renin secretion and renal function. Am J Physiol. 1970 Aug;219(2):455–459. doi: 10.1152/ajplegacy.1970.219.2.455. [DOI] [PubMed] [Google Scholar]
  31. Vander A. J. Effect of catecholamines and the renal nerves on renin secretion in anesthetized dogs. Am J Physiol. 1965 Sep;209(3):659–662. doi: 10.1152/ajplegacy.1965.209.3.659. [DOI] [PubMed] [Google Scholar]
  32. Vandongen R., Peart W. S., Boyd G. W. Andrenergic stimulation of renin secretion in the isolated perfused rat kidney. Circ Res. 1973 Feb;32(2):290–296. doi: 10.1161/01.res.32.2.290. [DOI] [PubMed] [Google Scholar]
  33. Weber M. A., Thornell I. R., Stokes G. S. Effect of hemorrhage with and without fluid replacement on plasma renin activity. Am J Physiol. 1973 Nov;225(5):1161–1164. doi: 10.1152/ajplegacy.1973.225.5.1161. [DOI] [PubMed] [Google Scholar]
  34. Weber M. A., Thornell I. R., Stokes G. S. Effects of beta adrenergic blocking agents on plasma renin activity in the conscious rabbit. J Pharmacol Exp Ther. 1974 Jan;188(1):234–240. [PubMed] [Google Scholar]
  35. Winer N., Chokshi D. S., Yoon M. S., Freedman A. D. Adrenergic receptor mediation of renin secretion. J Clin Endocrinol Metab. 1969 Sep;29(9):1168–1175. doi: 10.1210/jcem-29-9-1168. [DOI] [PubMed] [Google Scholar]
  36. ZIEGLER M., GROSS F. EFFECT OF BLOOD VOLUME CHANGES ON RENIN-LIKE ACTIVITY IN BLOOD. Proc Soc Exp Biol Med. 1964 Jul;116:774–778. doi: 10.3181/00379727-116-29370. [DOI] [PubMed] [Google Scholar]

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