An in vitro investigation of aorta and corpus cavernosum from eNOS and nNOS gene-deficient mice.
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.
Nangle
M R
MR
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD, Aberdeen, Scotland, UK.
Cotter
M A
MA
Cameron
N E
NE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010413:Penis / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D000109:Acetylcholine