An in vitro investigation of aorta and corpus cavernosum from eNOS and nNOS gene-deficient mice

Matthew Robert Nangle, Mary Anne Cotter, Norman E Cameron

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Abstract

In order to ascertain the relative contribution of the endothelial and neuronal nitric oxide (NO) synthase isoforms on NO-dependent vascular and nerve function in vitro, aorta and corpus cavernosum from mice deficient in their expression (eNOS-/- and nNOS-/-) were isolated in organ baths for tension measurements. Agonist or electrical field stimulation (EFS) evoked nerve-mediated responses were compared against wild-type controls. In aortas from nNOS-/- mice, contraction responses to phenylephrine were increased. Conversely, endothelium-dependent relaxation (EDR) to acetylcholine (ACh) was decreased. In contrast, eNOS-/- aortas showed decreased sensitivity to phenylephrine and developed a flurbiprofen-sensitive contraction to ACh, and sensitivity to the NO-donor sodium nitroprusside was increased. In cavernosum from eNOS-/- and nNOS-/- mice, maximum contractions to phenylephrine and EFS, and relaxation responses to nitroprusside, were increased. As in aorta, ACh addition led to a contractile response in eNOS-/- cavernosum. Maximum EFS induced non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation was increased in eNOS-/-, whilst being decreased in nNOS-/- cavernosum. These data suggest that whilst NO-dependent vascular function is primarily eNOS mediated, and nerve function nNOS mediated, aorta function may be at least partially reliant on nNOS-related mechanisms. In addition, mechanisms of physiological compensation were observed, which require further study.

Original languageEnglish
Pages (from-to)139-145
Number of pages6
JournalPflugers Archiv : European Journal of Physiology
Volume448
Issue number2
DOIs
Publication statusPublished - May 2004

Keywords

  • aorta
  • corpus cavernosum
  • endothelium
  • NANC nerve
  • nitric oxide
  • smooth muscle
  • NITRIC-OXIDE SYNTHASE
  • ACETYLCHOLINE-INDUCED RELAXATION
  • KNOCKOUT MICE
  • PENILE ERECTION
  • LACKING
  • RAT
  • FLOW
  • DILATION
  • ARTERIES
  • MOUSE

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