Role of Endothelium-Derived Hyperpolarizing Factor in ACE Inhibitor-Induced Renal Vasodilation in Vivo

Hiroto Matsuda, Koichi Hayashi, Shu Wakino, Eiji Kubota, Masanori Honda, Hirobumi Tokuyama, Ichiro Takamatsu, Satoru Tatematsu, Takao Saruta

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Although the angiotensin-converting enzyme (ACE) inhibitor-induced bradykinin enhances nitric oxide (NO) release, bradykinin may also stimulate the production of an additional vasodilator, endothelium-derived hyperpolarizing factor (EDHF). This study examined the role of EDHF in mediating the NO-independent action of ACE inhibitors in canine renal microcirculation in vivo. We used intravital CCD camera videomicroscopy that allowed direct visualization of renal microcirculation in superficial and juxtamedullary nephrons in an in vivo, in situ, and relatively intact setting. In the presence of E4177 (an angiotensin receptor blocker), cilazaprilat (30 μg/kg) had no effect on diameter of superficial afferent arterioles (Aff), but it increased renal contents of bradykinin and nitrate plus nitrite, and it elicited dilation of juxtamedullary Aff (from 24.0±0.2 to 28.2±0. 8 μm), juxtamedullary efferent arterioles (Eff) (from 24.2±0.2 to 28.0±0.8 μm), and superficial Eff (from 18.2±0.2 to 19.7±0.2 μm). These changes in diameters were prevented by N α-adamantaneacetyl-D-Arg-[Hyp3,Thi 5,8,D-Phe7]bradykinin, a bradykinin receptor antagonist. The pre-treatment with nitro-L-arginine methylester (L-NAME) plus E4177 eliminated the dilator response of juxtamedullary/superficial Eff and the increase in renal nitrate plus nitrite levels induced by cilazaprilat. In contrast, in the presence of E4177+L-NAME, cilazaprilat still caused 8%±3% dilation of juxtamedullary Aff, which was completely eliminated by proadifen, a cytochrome-P450 and KCa channel blocker. Collectively, the ACE inhibitor exerts multiple vasodilator mechanisms, including the inhibition of angiotensin II formation; blockade of angiotensin II activity appears to be a dominant mechanism in superficial Aff, whereas the bradykinin-induced NO acts on superficial Eff and juxtamedullary Aff/Eff. Furthermore, a putative EDHF is an additional mechanism for the ACE inhibitor-induced vasodilation of juxtamedullary Aff in vivo.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalHypertension
Volume43
Issue number3
DOIs
Publication statusPublished - 2004 Mar

Fingerprint

Bradykinin
Angiotensin-Converting Enzyme Inhibitors
Vasodilation
Endothelium
Kidney
Nitric Oxide
NG-Nitroarginine Methyl Ester
Arterioles
Microcirculation
Nitrites
Vasodilator Agents
Angiotensin II
Nitrates
Dilatation
Proadifen
Video Microscopy
Angiotensin Receptor Antagonists
Nephrons
Cytochrome P-450 Enzyme System
Arginine

Keywords

  • Angiotensin-converting enzyme
  • Arterioles
  • Bradykinin
  • Endothelium-derived factors
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Role of Endothelium-Derived Hyperpolarizing Factor in ACE Inhibitor-Induced Renal Vasodilation in Vivo. / Matsuda, Hiroto; Hayashi, Koichi; Wakino, Shu; Kubota, Eiji; Honda, Masanori; Tokuyama, Hirobumi; Takamatsu, Ichiro; Tatematsu, Satoru; Saruta, Takao.

In: Hypertension, Vol. 43, No. 3, 03.2004, p. 603-609.

Research output: Contribution to journalArticle

Matsuda, Hiroto ; Hayashi, Koichi ; Wakino, Shu ; Kubota, Eiji ; Honda, Masanori ; Tokuyama, Hirobumi ; Takamatsu, Ichiro ; Tatematsu, Satoru ; Saruta, Takao. / Role of Endothelium-Derived Hyperpolarizing Factor in ACE Inhibitor-Induced Renal Vasodilation in Vivo. In: Hypertension. 2004 ; Vol. 43, No. 3. pp. 603-609.
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