An in vitro study of corpus cavernosum and aorta from mice lacking the inducible nitric oxide synthase gene.
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.
School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Matthew R
MR
Nangle
Mary A
MA
Cotter
Norman E
NE
Cameron
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005480:Flurbiprofen / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000201:enzymology* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D016861:Cyclooxygenase Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D005480:Flurbiprofen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000109:Acetylcholine