Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: Role of intrarenal bradykinin

Hiroto Matsuda, Koichi Hayashi, Koki Arakawa, Mareo Naitoh, Eiji Kubota, Masanori Honda, Akira Matsumoto, Hiromichi Suzuki, Tokunori Yamamoto, Fumihiko Kajiya, Takao Saruta

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The present study examined the role of intrarenal bradykinin in angiotensin-converting enzyme inhibitor (ACEI)-induced dilation of renal afferent (AFF) and efferent arterioles (EFF) in vivo, and further evaluated whether ACEI-stimulated bradykinin activity differed in superficial (SP) and juxtamedullary nephrons (JM). Arterioles of canine kidneys were visualized with an intravital charge-coupled device camera microscope. E4177 (an angiotensin receptor antagonist, 30 μg/kg) dilated AFF and EFF in SP (15 ± 3% and 19 ± 5%) and JM (15 ± 3% and 18 ± 4%). Subsequently, cilazaprilat (30 μg/kg) caused further dilation of both AFF (29 ± 4%) and EFF (36 ± 4%) in JM, whereas in SP it dilated only EFF (29 ± 3%). Similarly, in the presence of E4177, cilazaprilat caused further increases in sodium excretion. This cilazaprilat-induced vasodilation and natriuresis was abolished by a bradykinin antagonist (N(α)-adamantaneacetyl-D-Arg-[Hyp3,Thi5.8,D- Phe7]bradykinin). In parallel with these results, cilazaprilat increased renal bradykinin content, more greatly in the medulla than in the cortex (5.7 ± 0.4 versus 4.6 ± 0.1 ng/g). Similarly, cilazaprilat elicited greater bradykinin-dependent increases of nitrite/nitrate in the medulla. In conclusion, zonal heterogeneity in renal bradykinin/nitric oxide levels and segmental differences in reactivity to bradykinin contribute to the diverse responsiveness of renal AFF and EFF to ACEI. ACEI-enhanced kinin action would participate in the amelioration of glomerular hemodynamics and renal sodium excretion by ACEI.

Original languageEnglish
Pages (from-to)2272-2282
Number of pages11
JournalJournal of the American Society of Nephrology
Volume10
Issue number11
Publication statusPublished - 1999 Nov

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: Role of intrarenal bradykinin'. Together they form a unique fingerprint.

  • Cite this

    Matsuda, H., Hayashi, K., Arakawa, K., Naitoh, M., Kubota, E., Honda, M., Matsumoto, A., Suzuki, H., Yamamoto, T., Kajiya, F., & Saruta, T. (1999). Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: Role of intrarenal bradykinin. Journal of the American Society of Nephrology, 10(11), 2272-2282.