Low-Dose Combination Therapy with Temocapril and Losartan Reduces Proteinuria in Normotensive Patients with Immunoglobulin A Nephropathy

Horita, Yuki; Tadokoro, Masato; Taura, Koichi; Suyama, Naofumi; Taguchi, Takashi; Miyazaki, Masanobu; Kohno, Shigeru

doi:10.1291/hypres.27.963

Cited by 55 publications

(45 citation statements)

References 30 publications

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“…Beyond normalization, these agents do not produce any hypotensive effect in either CV or IAS hypertension in SHR. This is in agreement with previous reports showing the absence of adverse effects of captopril and losartan in normotensive rats and humans (Lee et al, 1991;Horita et al, 2004;Cosentino et al, 2005).…”

Section: Discussionsupporting

confidence: 94%

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Godoy

Rattan

2006

J Pharmacol Exp Ther

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The present study determined the effects of the angiotensinconverting enzyme (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT 1 -R) antagonist losartan on the internal anal sphincter pressures (IASP) in spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats (WKY). The SHR had significantly higher IASP (21.7 Ϯ 0.8 mm Hg) than the WKY (14.7 Ϯ 0.9 mm Hg), which was associated with the higher levels of angiotensin II (Ang II) in plasma (50.3 Ϯ 0.9 pg/ml) and in muscle bath perfusates (72.7 Ϯ 11.8 pg/ml) compared with the WKY (p Ͻ 0.05). Captopril and losartan decreased the IASP in SHR and WKY, but they were more potent in SHR. Captopril and losartan normalized the IASP in the SHR, whereas these agents may compromise rectoanal continence in the WKY. Reverse transcriptase-polymerase chain reaction and Western blots showed higher levels of angiotensinogen, renin, ACE, and AT 1 -R in the internal anal sphincter (IAS) of SHR. Ang II caused concentration-dependent contraction of IAS smooth muscle strips from WKY (pEC 50 ϭ 8.5 Ϯ 0.1) and SHR (pEC 50 ϭ 8.6 Ϯ 0.2). Losartan (100 nM) significantly (p Ͻ 0.05) inhibited this effect. From these data, we conclude that 1) hypertensive IAS in SHR is primarily the result of renin-angiotensin system upregulation, 2) ACE inhibitors and AT 1 -R antagonists simply relieve the hypertensive IAS, and 3) the differential effect of these inhibitors in the hypertensive versus the normotensive IAS may explain the lack of incontinence as a side effect in hypertensive patients receiving ACE inhibitors and AT 1 -R antagonists.Earlier studies from our laboratory have put forward evidence for the role of angiotensin II (Ang II) biosynthesis in the spontaneous myogenic tone of the internal anal sphincter (IAS) of rats (De Godoy et al., 2004). The studies show the expression of key components of the renin-angiotensin system (RAS

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Section: Discussionsupporting

confidence: 94%

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Godoy

Rattan

2006

J Pharmacol Exp Ther

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“…It has been shown that both ACEIs and ARBs confer renal protection by reducing blood pressure (BP) and also by certain other mechanisms independent of their BP-lowering action. It has also been reported that low-dose combination therapy with ACEI temocapril and ARB losartan reduced proteinuria in normotensive patients with immunoglobulin A nephropathy (5).…”

Section: Introductionmentioning

confidence: 90%

Effects of Monotherapy of Temocapril or Candesartan with Dose Increments or Combination Therapy with Both Drugs on the Suppression of Diabetic Nephropathy

et al. 2007

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“…8 In addition, clinical and experimental studies have demonstrated that blockade of the RAS successfully alleviates the symptoms of IgAN. 9 These evidence suggest a role for the activated RAS in the development of IgAN. Angiotensinogen (AGT) interacted with renin to produce angiotensin I, which was then catalyzed to form angiotensin II.…”

Section: Introductionmentioning

confidence: 90%

Association of angiotensinogen gene M235T polymorphism with the risk of IgA nephropathy: a meta-analysis

Mao

Huang

2013

Renal Failure

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The association between angiotensinogen (AGT) M235T gene polymorphism and IgA nephropathy (IgAN) risk remains elusive. Our aim was to evaluate the association between AGT M235T gene polymorphism and IgAN susceptibility by performing a meta-analysis. Eligible studies were searched according to predefined criteria using electronic databases. Eight studies were identified for the analysis of the association between AGT M235T gene polymorphism and

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Low-Dose Combination Therapy with Temocapril and Losartan Reduces Proteinuria in Normotensive Patients with Immunoglobulin A Nephropathy

Cited by 55 publications

References 30 publications

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Effects of Monotherapy of Temocapril or Candesartan with Dose Increments or Combination Therapy with Both Drugs on the Suppression of Diabetic Nephropathy

Association of angiotensinogen gene M235T polymorphism with the risk of IgA nephropathy: a meta-analysis

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