Effects of angiotensin-converting enzyme inhibitor and α1- adrenoceptor antagonist on hypertension induced in rats by long- term inhibition of nitric oxide production

M. Takahashi, Fumio Otsuka, T. Ogura, T. Yamauchi, H. Kataoka, M. Kishida, Yukari Mimura, Hirofumi Makino

Research output: Contribution to journalArticle

Abstract

Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalClinical and Experimental Nephrology
Volume4
Issue number2
Publication statusPublished - 2000

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Cilazapril
Angiotensin-Converting Enzyme Inhibitors
Adrenergic Receptors
Nitric Oxide
Doxazosin
Hypertension
Blood Pressure
Kidney
Sympathetic Nervous System
Wounds and Injuries
Sclerosis
Renin-Angiotensin System
Nitrites
Aldosterone
Nitrates
Sprague Dawley Rats
Arginine

Keywords

  • Cilazapril
  • Doxazosin
  • N(G)-nitro-L-arginine
  • Nitric oxide

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Effects of angiotensin-converting enzyme inhibitor and α1- adrenoceptor antagonist on hypertension induced in rats by long- term inhibition of nitric oxide production",
abstract = "Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.",
keywords = "Cilazapril, Doxazosin, N(G)-nitro-L-arginine, Nitric oxide",
author = "M. Takahashi and Fumio Otsuka and T. Ogura and T. Yamauchi and H. Kataoka and M. Kishida and Yukari Mimura and Hirofumi Makino",
year = "2000",
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TY - JOUR

T1 - Effects of angiotensin-converting enzyme inhibitor and α1- adrenoceptor antagonist on hypertension induced in rats by long- term inhibition of nitric oxide production

AU - Takahashi, M.

AU - Otsuka, Fumio

AU - Ogura, T.

AU - Yamauchi, T.

AU - Kataoka, H.

AU - Kishida, M.

AU - Mimura, Yukari

AU - Makino, Hirofumi

PY - 2000

Y1 - 2000

N2 - Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.

AB - Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.

KW - Cilazapril

KW - Doxazosin

KW - N(G)-nitro-L-arginine

KW - Nitric oxide

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