Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Oct;119(4):744–750. doi: 10.1111/j.1476-5381.1996.tb15735.x

Effect of amlodipine on renin secretion and renin gene expression in rats.

K Schricker 1, M Hamann 1, A Macher 1, B K Krämer 1, B Kaissling 1, A Kurtz 1
PMCID: PMC1915752  PMID: 8904650

Abstract

1. This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA levels in normal rats and rats with unilateral renal hypoperfusion induced by applying 0.2 mm left renal artery clips over four days. 2. In normotensive rats, amlodipine significantly decreased basal blood pressure by about 20 mmHg when applied in a concentration of 5, 15 and 45 mg kg-1. Plasma renin activity and also renin mRNA levels were not changed after application of 5 mg kg-1 of amlodipine. However, at a concentration of 15 or 45 mg kg-1, amlodipine, significantly increased not only plasma renin activity by about 250% and 300%, but also renin mRNA levels by about 100% and 500%. The action of amlodipine on all these parameters was maximal after 24 h. Treatment with amlodipine in a concentration of 15 mg kg-1 also increased renin immunoreactive areas in the kidney cortex by retrograde recruitment of renin expressing cells in the afferent arterioles. 3. In 2kidney-1 clip rats, systolic blood pressure rose continuously whilst plasma renin activity and renin m-RNA in the clipped kidney increased transiently and renin m-RNA in the contralateral kidney was constantly suppressed. Amlodipine at a concentration of 15 mg kg-1 markedly attenuated the increase of blood pressure in 2kidney-1 clip rats, produced an almost additive effect on plasma renin activity and showed a tendency to increase renin m-RNA levels in the clipped kidneys. Renin m-RNA levels in the contralateral kidney were also significantly suppressed in the animals receiving additional treatment with amlodipine. 4. These findings suggest that inhibition of calcium channels by amlodipine stimulates renin secretion and renin gene expression in vivo. These stimulatory effects are almost additive to the changes of renin secretion occurring after an unilateral fall of renal perfusion pressure.

Full text

PDF
744

Selected References

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

  1. Antonipillai I., Horton R. Role of extra- and intracellular calcium and calmodulin in renin release from rat kidney. Endocrinology. 1985 Aug;117(2):601–606. doi: 10.1210/endo-117-2-601. [DOI] [PubMed] [Google Scholar]
  2. Burnham C. E., Hawelu-Johnson C. L., Frank B. M., Lynch K. R. Molecular cloning of rat renin cDNA and its gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5605–5609. doi: 10.1073/pnas.84.16.5605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cappuccio F. P., Markandu N. D., Sagnella G. A., Singer D. R., Buckley M. G., Miller M. A., MacGregor G. A. Effects of amlodipine on urinary sodium excretion, renin-angiotensin-aldosterone system, atrial natriuretic peptide and blood pressure in essential hypertension. J Hum Hypertens. 1991 Apr;5(2):115–119. [PubMed] [Google Scholar]
  4. Cappuccio F. P., Markandu N. D., Singer D. R., MacGregor G. A. Amlodipine and lisinopril in combination for the treatment of essential hypertension: efficacy and predictors of response. J Hypertens. 1993 Aug;11(8):839–847. doi: 10.1097/00004872-199308000-00011. [DOI] [PubMed] [Google Scholar]
  5. Cauvin C., Loutzenhiser R., Van Breemen C. Mechanisms of calcium antagonist-induced vasodilation. Annu Rev Pharmacol Toxicol. 1983;23:373–396. doi: 10.1146/annurev.pa.23.040183.002105. [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Cobbin L. B., Einstein R., Maguire M. H. Studies on the coronary dilator actions of some adenosine analogues. Br J Pharmacol. 1974 Jan;50(1):25–33. doi: 10.1111/j.1476-5381.1974.tb09589.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dawson T. P., Gandhi R., Le Hir M., Kaissling B. Ecto-5'-nucleotidase: localization in rat kidney by light microscopic histochemical and immunohistochemical methods. J Histochem Cytochem. 1989 Jan;37(1):39–47. doi: 10.1177/37.1.2535703. [DOI] [PubMed] [Google Scholar]
  9. Della Bruna R., Pinet F., Corvol P., Kurtz A. Opposite regulation of renin gene expression by cyclic AMP and calcium in isolated mouse juxtaglomerular cells. Kidney Int. 1995 May;47(5):1266–1273. doi: 10.1038/ki.1995.181. [DOI] [PubMed] [Google Scholar]
  10. Fray J. C., Park C. S. Influence of potassium, sodium, perfusion pressure, and isoprenaline on renin release induced by acute calcium deprivation. J Physiol. 1979 Jul;292:363–372. doi: 10.1113/jphysiol.1979.sp012856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fray J. C. Stretch receptor model for renin release with evidence from perfused rat kidney. Am J Physiol. 1976 Sep;231(3):936–944. doi: 10.1152/ajplegacy.1976.231.3.936. [DOI] [PubMed] [Google Scholar]
  12. Hackenthal E., Paul M., Ganten D., Taugner R. Morphology, physiology, and molecular biology of renin secretion. Physiol Rev. 1990 Oct;70(4):1067–1116. doi: 10.1152/physrev.1990.70.4.1067. [DOI] [PubMed] [Google Scholar]
  13. Holmer S., Eckardt K. U., Aedtner O., LeHir M., Schricker K., Hamann M., Götz K., Riegger G., Moll W., Kurtz A. Which factor mediates reno-renal control of renin gene expression? J Hypertens. 1993 Oct;11(10):1011–1019. doi: 10.1097/00004872-199310000-00003. [DOI] [PubMed] [Google Scholar]
  14. Johns E. J. A study of the renal actions of amlodipine in the normotensive and spontaneously hypertensive rat. Br J Pharmacol. 1988 Jun;94(2):311–318. doi: 10.1111/j.1476-5381.1988.tb11532.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jones-Dombi T., Churchill P. The baroreceptor mechanism for controlling renin secretion: effect of calcium channel blockers. J Pharmacol Exp Ther. 1993 Jul;266(1):274–278. [PubMed] [Google Scholar]
  16. Letizia C., De Ciocchis A., Cerci S., Coassin S., Fisher H., Tarsitani P., Scavo D. Amlodipine in ambulatory hypertensive patients: humoral and haemodynamic effects. Int J Clin Pharmacol Res. 1993;13(3):151–159. [PubMed] [Google Scholar]
  17. Licata G., Scaglione R., Ganguzza A., Parrinello G., Costa R., Merlino G., Corrao S., Amato P. Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive patients. A randomized controlled study versus placebo. Eur J Clin Pharmacol. 1993;45(4):307–311. doi: 10.1007/BF00265946. [DOI] [PubMed] [Google Scholar]
  18. Mattes A., Lemmer B. Effects of amlodipine on circadian rhythms in blood pressure, heart rate, and motility: a telemetric study in rats. Chronobiol Int. 1991;8(6):526–538. doi: 10.3109/07420529109059188. [DOI] [PubMed] [Google Scholar]
  19. Morel N., Godfraind T. Selective interaction of the calcium antagonist amlodipine with calcium channels in arteries of spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1994 Oct;24(4):524–533. doi: 10.1097/00005344-199410000-00002. [DOI] [PubMed] [Google Scholar]
  20. Reams G. P., Lau A., Hamory A., Bauer J. H. Amlodipine therapy corrects renal abnormalities encountered in the hypertensive state. Am J Kidney Dis. 1987 Dec;10(6):446–451. doi: 10.1016/s0272-6386(87)80191-9. [DOI] [PubMed] [Google Scholar]
  21. Scholz H., Hamann M., Götz K. H., Kurtz A. Role of calcium ions in the pressure control of renin secretion from the kidneys. Pflugers Arch. 1994 Sep;428(2):173–178. doi: 10.1007/BF00374855. [DOI] [PubMed] [Google Scholar]
  22. Scholz H., Kurtz A. Differential regulation of cytosolic calcium between afferent arteriol ar smooth muscle cells from mouse kidney. Pflugers Arch. 1995 Nov;431(1):46–51. doi: 10.1007/BF00374376. [DOI] [PubMed] [Google Scholar]
  23. Schricker K., Hamann M., Kaissling B., Kurtz A. Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats. Pflugers Arch. 1994 May;427(1-2):42–46. doi: 10.1007/BF00585940. [DOI] [PubMed] [Google Scholar]
  24. Schricker K., Holmer S., Hamann M., Riegger G., Kurtz A. Interrelation between renin mRNA levels, renin secretion, and blood pressure in two-kidney, one clip rats. Hypertension. 1994 Aug;24(2):157–162. doi: 10.1161/01.hyp.24.2.157. [DOI] [PubMed] [Google Scholar]
  25. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES