Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Oct 15;100(8):2107–2114. doi: 10.1172/JCI119745

Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.

T Takenaka 1, H Suzuki 1, K Fujiwara 1, Y Kanno 1, Y Ohno 1, K Hayashi 1, T Nagahama 1, T Saruta 1
PMCID: PMC508403  PMID: 9329977

Abstract

To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29+/-3 (n = 8, P < 0.01) and 27+/-3% (n = 8, P < 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65+/-9% (P < 0.01). In the second group, the addition of N-ethylmaleimide (10 microM), a Gi/Go protein antagonist, abolished AngII- induced EA (n = 6) but not AA constriction (n = 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 microM), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII (n = 6 for each). In the fourth group, thapsigargin (1 microM) prevented AngII-induced AA constriction (n = 8) and attenuated EA constriction (8+/-2% decrease in EA diameter at 0.3 nM AngII, n = 8, P < 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry.

Full Text

The Full Text of this article is available as a PDF (186.5 KB).

Selected References

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

  1. Anderson S., Rennke H. G., Brenner B. M. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986 Jun;77(6):1993–2000. doi: 10.1172/JCI112528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
  3. Bigay J., Deterre P., Pfister C., Chabre M. Fluoroaluminates activate transducin-GDP by mimicking the gamma-phosphate of GTP in its binding site. FEBS Lett. 1985 Oct 28;191(2):181–185. doi: 10.1016/0014-5793(85)80004-1. [DOI] [PubMed] [Google Scholar]
  4. Birnbaumer L., Abramowitz J., Brown A. M. Receptor-effector coupling by G proteins. Biochim Biophys Acta. 1990 May 7;1031(2):163–224. doi: 10.1016/0304-4157(90)90007-y. [DOI] [PubMed] [Google Scholar]
  5. Blantz R. C., Konnen K. S., Tucker B. J. Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat. J Clin Invest. 1976 Feb;57(2):419–434. doi: 10.1172/JCI108293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carmines P. K., Fowler B. C., Bell P. D. Segmentally distinct effects of depolarization on intracellular [Ca2+] in renal arterioles. Am J Physiol. 1993 Nov;265(5 Pt 2):F677–F685. doi: 10.1152/ajprenal.1993.265.5.F677. [DOI] [PubMed] [Google Scholar]
  7. Carmines P. K., Navar L. G. Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II. Am J Physiol. 1989 Jun;256(6 Pt 2):F1015–F1020. doi: 10.1152/ajprenal.1989.256.6.F1015. [DOI] [PubMed] [Google Scholar]
  8. Conger J. D., Falk S. A., Robinette J. B. Angiotensin II-induced changes in smooth muscle calcium in rat renal arterioles. J Am Soc Nephrol. 1993 May;3(11):1792–1803. doi: 10.1681/ASN.V3111792. [DOI] [PubMed] [Google Scholar]
  9. Dzau V. J., Colucci W. S., Williams G. H., Curfman G., Meggs L., Hollenberg N. K. Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure. N Engl J Med. 1980 Jun 19;302(25):1373–1379. doi: 10.1056/NEJM198006193022501. [DOI] [PubMed] [Google Scholar]
  10. Gordienko D. V., Clausen C., Goligorsky M. S. Ionic currents and endothelin signaling in smooth muscle cells from rat renal resistance arteries. Am J Physiol. 1994 Feb;266(2 Pt 2):F325–F341. doi: 10.1152/ajprenal.1994.266.2.F325. [DOI] [PubMed] [Google Scholar]
  11. Hishikawa K., Nakaki T., Marumo T., Hayashi M., Suzuki H., Kato R., Saruta T. Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells. J Clin Invest. 1994 May;93(5):1975–1980. doi: 10.1172/JCI117189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ichikawa I., Miele J. F., Brenner B. M. Reversal of renal cortical actions of angiotensin II by verapamil and manganese. Kidney Int. 1979 Aug;16(2):137–147. doi: 10.1038/ki.1979.115. [DOI] [PubMed] [Google Scholar]
  13. Ichikawi I., Harris R. C. Angiotensin actions in the kidney: renewed insight into the old hormone. Kidney Int. 1991 Oct;40(4):583–596. doi: 10.1038/ki.1991.249. [DOI] [PubMed] [Google Scholar]
  14. Ikenaga H., Fallet R. W., Carmines P. K. Contribution of tubuloglomerular feedback to renal arteriolar angiotensin II responsiveness. Kidney Int. 1996 Jan;49(1):34–39. doi: 10.1038/ki.1996.5. [DOI] [PubMed] [Google Scholar]
  15. Ito S., Johnson C. S., Carretero O. A. Modulation of angiotensin II-induced vasoconstriction by endothelium-derived relaxing factor in the isolated microperfused rabbit afferent arteriole. J Clin Invest. 1991 May;87(5):1656–1663. doi: 10.1172/JCI115181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jakobs K. H., Lasch P., Minuth M., Aktories K., Schultz G. Uncoupling of alpha-adrenoceptor-mediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem. 1982 Mar 25;257(6):2829–2833. [PubMed] [Google Scholar]
  17. Jensen B. L., Skøtt O. Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles. Am J Physiol. 1996 May;270(5 Pt 2):F718–F727. doi: 10.1152/ajprenal.1996.270.5.F718. [DOI] [PubMed] [Google Scholar]
  18. Komori S., Bolton T. B. Calcium release induced by inositol 1,4,5-trisphosphate in single rabbit intestinal smooth muscle cells. J Physiol. 1991 Feb;433:495–517. doi: 10.1113/jphysiol.1991.sp018440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kurtz A., Penner R. Effects of angiotensin II on intracellular calcium and electrical function of mouse renal juxtaglomerular cells. Kidney Int Suppl. 1990 Nov;30:S51–S54. [PubMed] [Google Scholar]
  20. Liebau S., Hohlfeld J., Förstermann U. The inhibition of alpha 1-adrenoceptor-mediated contractions of rabbit pulmonary artery by Ca2+-withdrawal, pertussis toxin and N-ethylmaleimide is dependent on agonist intrinsic efficacy. Naunyn Schmiedebergs Arch Pharmacol. 1989 May;339(5):496–502. doi: 10.1007/BF00167251. [DOI] [PubMed] [Google Scholar]
  21. Loutzenhiser R., Epstein M., Hayashi K., Takenaka T., Forster H. Characterization of the renal microvascular effects of angiotensin II antagonist, DuP 753: studies in isolated perfused hydronephrotic kidneys. Am J Hypertens. 1991 Apr;4(4 Pt 2):309S–314S. doi: 10.1093/ajh/4.4.309s. [DOI] [PubMed] [Google Scholar]
  22. Loutzenhiser R., Hayashi K., Epstein M. Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney. J Pharmacol Exp Ther. 1988 Aug;246(2):522–528. [PubMed] [Google Scholar]
  23. Loutzenhiser R., Hayashi K., Epstein M. Divergent effects of KCl-induced depolarization on afferent and efferent arterioles. Am J Physiol. 1989 Oct;257(4 Pt 2):F561–F564. doi: 10.1152/ajprenal.1989.257.4.F561. [DOI] [PubMed] [Google Scholar]
  24. Lu S., Mattson D. L., Cowley A. W., Jr Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats. Hypertension. 1994 Mar;23(3):337–345. doi: 10.1161/01.hyp.23.3.337. [DOI] [PubMed] [Google Scholar]
  25. Ohya Y., Sperelakis N. Involvement of a GTP-binding protein in stimulating action of angiotensin II on calcium channels in vascular smooth muscle cells. Circ Res. 1991 Mar;68(3):763–771. doi: 10.1161/01.res.68.3.763. [DOI] [PubMed] [Google Scholar]
  26. Oike M., Kitamura K., Kuriyama H. Protein kinase C activates the non-selective cation channel in the rabbit portal vein. Pflugers Arch. 1993 Jul;424(2):159–164. doi: 10.1007/BF00374607. [DOI] [PubMed] [Google Scholar]
  27. Pfeilschifter J., Bauer C. Pertussis toxin abolishes angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells. Biochem J. 1986 May 15;236(1):289–294. doi: 10.1042/bj2360289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ruan X., Arendshorst W. J. Calcium entry and mobilization signaling pathways in ANG II-induced renal vasoconstriction in vivo. Am J Physiol. 1996 Mar;270(3 Pt 2):F398–F405. doi: 10.1152/ajprenal.1996.270.3.F398. [DOI] [PubMed] [Google Scholar]
  29. Rüegg U. T., Wallnöfer A., Weir S., Cauvin C. Receptor-operated calcium-permeable channels in vascular smooth muscle. J Cardiovasc Pharmacol. 1989;14 (Suppl 6):S49–S58. [PubMed] [Google Scholar]
  30. Schnermann J., Briggs J. Role of the renin-angiotensin system in tubuloglomerular feedback. Fed Proc. 1986 Apr;45(5):1426–1430. [PubMed] [Google Scholar]
  31. Schultz G., Rosenthal W., Hescheler J., Trautwein W. Role of G proteins in calcium channel modulation. Annu Rev Physiol. 1990;52:275–292. doi: 10.1146/annurev.ph.52.030190.001423. [DOI] [PubMed] [Google Scholar]
  32. Steinhausen M., Snoei H., Parekh N., Baker R., Johnson P. C. Hydronephrosis: a new method to visualize vas afferens, efferens, and glomerular network. Kidney Int. 1983 Jun;23(6):794–806. doi: 10.1038/ki.1983.98. [DOI] [PubMed] [Google Scholar]
  33. Takenaka T., Forster H. Arginine vasopressin interacts with thromboxane in hydronephrosis. Am J Physiol. 1997 Jan;272(1 Pt 2):F40–F47. doi: 10.1152/ajprenal.1997.272.1.F40. [DOI] [PubMed] [Google Scholar]
  34. Takenaka T., Forster H., Epstein M. Characterization of the renal microvascular actions of a new dopaminergic (DA1) agonist, YM435. J Pharmacol Exp Ther. 1993 Mar;264(3):1154–1159. [PubMed] [Google Scholar]
  35. Takenaka T., Forster H., Epstein M. Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin. Circ Res. 1993 Oct;73(4):743–750. doi: 10.1161/01.res.73.4.743. [DOI] [PubMed] [Google Scholar]
  36. Takenaka T., Hashimoto Y., Epstein M. Diminished acetylcholine-induced vasodilation in renal microvessels of cyclosporine-treated rats. J Am Soc Nephrol. 1992 Jul;3(1):42–50. doi: 10.1681/ASN.V3142. [DOI] [PubMed] [Google Scholar]
  37. Takenaka T., Kanno Y., Kitamura Y., Hayashi K., Suzuki H., Saruta T. Role of chloride channels in afferent arteriolar constriction. Kidney Int. 1996 Sep;50(3):864–872. doi: 10.1038/ki.1996.386. [DOI] [PubMed] [Google Scholar]
  38. Takenaka T., Suzuki H., Furukawa T., Ogata Y., Saruta T. Role of intrarenal renin-angiotensin system on pressure-natriuresis in spontaneously hypertensive rats. Clin Exp Hypertens A. 1990;12(8):1377–1394. doi: 10.3109/10641969009073525. [DOI] [PubMed] [Google Scholar]
  39. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  40. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Van Renterghem C., Lazdunski M. Identification of the Ca2+ current activated by vasoconstrictors in vascular smooth muscle cells. Pflugers Arch. 1994 Nov;429(1):1–6. doi: 10.1007/BF02584023. [DOI] [PubMed] [Google Scholar]
  42. Weber L. P., Chow W. L., Abebe W., MacLeod K. M. Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. Br J Pharmacol. 1996 May;118(1):115–122. doi: 10.1111/j.1476-5381.1996.tb15373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. de Gasparo M., Husain A., Alexander W., Catt K. J., Chiu A. T., Drew M., Goodfriend T., Harding J. W., Inagami T., Timmermans P. B. Proposed update of angiotensin receptor nomenclature. Hypertension. 1995 May;25(5):924–927. doi: 10.1161/01.hyp.25.5.924. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES