An in vitro study of corpus cavernosum and aorta from mice lacking the inducible nitric oxide synthase gene

Matthew Robert Nangle, Mary Anne Cotter, Norman E Cameron

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Nitric oxide (NO), produced by NO-synthase (NOS), serves as an important vasodilator and inhibitory neurotransmitter. Inducible NOS (iNOS) is expressed in response to cytokine stimulation and is therefore not ordinarily present in healthy tissue. However, iNOS has been identified in certain organs, including the penis. The development of mice deficient in the iNOS gene (iNOS -/-) has provided a useful tool for the study of iNOS function. Therefore, an in vitro examination of vascular and nerve-mediated responses of corpus cavernosum (CC) and vascular responses of aorta from iNOS -/- mice and their wild-type controls was undertaken. Tissues were mounted in organ baths for agonist- and/or electrical field stimulation (EFS)-induced responses under isometric tension. CC from iNOS -/- mice developed increased sensitivity to phenylephrine (PE) and an increased maximum EFS-induced noradrenergic contraction of approximately 31%. Following PE precontraction, maximum relaxation to acetylcholine was reduced by approximately 39%; conversely, there was a 23% increase in relaxation to the NO-donor sodium nitroprusside. EFS-induced non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation was unaltered compared to control. Agonist-induced responses of aorta did not significantly differ between iNOS -/- and control mice. These results suggest that iNOS-derived NO may play a role in modulating erectile function and confirm that iNOS does not play a significant role in macrovascular function under normal physiological conditions. (C) 2004 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)194-200
Number of pages6
JournalNitric Oxide: Biology and Chemistry
Volume9
Issue number4
DOIs
Publication statusPublished - 2003

Keywords

  • nitric oxide
  • endothelium
  • smooth muscle
  • iNOS
  • aorta
  • corpus cavernosum
  • smooth muscle cells
  • penile erection
  • endothelial cells
  • MESSENGER-RNA
  • knockout mice
  • expression
  • rat
  • responses
  • tissue
  • hypercholesterolemia

Cite this

An in vitro study of corpus cavernosum and aorta from mice lacking the inducible nitric oxide synthase gene. / Nangle, Matthew Robert; Cotter, Mary Anne; Cameron, Norman E.

In: Nitric Oxide: Biology and Chemistry, Vol. 9, No. 4, 2003, p. 194-200.

Research output: Contribution to journalArticle

Nangle, Matthew Robert ; Cotter, Mary Anne ; Cameron, Norman E. / An in vitro study of corpus cavernosum and aorta from mice lacking the inducible nitric oxide synthase gene. In: Nitric Oxide: Biology and Chemistry. 2003 ; Vol. 9, No. 4. pp. 194-200.
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AB - Nitric oxide (NO), produced by NO-synthase (NOS), serves as an important vasodilator and inhibitory neurotransmitter. Inducible NOS (iNOS) is expressed in response to cytokine stimulation and is therefore not ordinarily present in healthy tissue. However, iNOS has been identified in certain organs, including the penis. The development of mice deficient in the iNOS gene (iNOS -/-) has provided a useful tool for the study of iNOS function. Therefore, an in vitro examination of vascular and nerve-mediated responses of corpus cavernosum (CC) and vascular responses of aorta from iNOS -/- mice and their wild-type controls was undertaken. Tissues were mounted in organ baths for agonist- and/or electrical field stimulation (EFS)-induced responses under isometric tension. CC from iNOS -/- mice developed increased sensitivity to phenylephrine (PE) and an increased maximum EFS-induced noradrenergic contraction of approximately 31%. Following PE precontraction, maximum relaxation to acetylcholine was reduced by approximately 39%; conversely, there was a 23% increase in relaxation to the NO-donor sodium nitroprusside. EFS-induced non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation was unaltered compared to control. Agonist-induced responses of aorta did not significantly differ between iNOS -/- and control mice. These results suggest that iNOS-derived NO may play a role in modulating erectile function and confirm that iNOS does not play a significant role in macrovascular function under normal physiological conditions. (C) 2004 Elsevier Inc. All rights reserved.

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KW - iNOS

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KW - endothelial cells

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KW - knockout mice

KW - expression

KW - rat

KW - responses

KW - tissue

KW - hypercholesterolemia

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