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1 Division of Pediatric Cardiology, Mayo Clinic Rochester, Rochester, MN, USA
2 Department of Surgery, Mayo Clinic Rochester, Rochester, MN, USA
3 Department of Physiology and Biophysics, Mayo Clinic Rochester, Rochester, MN, USA
4 Department of Surgery, Mayo Clinic Rochester, Rochester, MN, USA; Department of Physiology and Biophysics, Mayo Clinic Rochester, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: miller.virginia{at}mayo.edu.
Cardiovascular disease begins in young adulthood and is more prevalent in males than females. However, little is known about vascular function during transition to adulthood in males. The aim of this study was to define changes in production of endothelium-derived nitric oxide and coronary arterial responses during puberty. Plasma was collected from juvenile (2-3 mo) and adult (5-6 mo) male pigs (n = 8/group) for measurement of nitric oxide and aortic endothelial cells were collected for measurement of mRNA and protein for endothelial nitric oxide synthase (eNOS). Although plasma NO was higher in juvenile (67.0 ± 25.6 µM) compared to adult (15.0 ± 7.1 µM) male pigs, eNOS protein was similar in both groups. However, mRNA for eNOS was lower in aortic endothelial cells from juvenile pigs. In rings of coronary arteries suspended in organ chambers for measurement of isometric force and contracted with prostaglandin F2
, relaxations to an 2-adrenergic agonist were significantly inhibited by indomethacin only in juvenile pigs [EC50 (-logM): 6.7 ± 0.3 with indomethacin and 7.7 ± 0.3 under control conditions]. NG-monomethyl-L-arginine (L-NMMA) inhibited relaxations in both groups. On the contrary, in the presence of indomethacin, relaxations to bradykinin were inhibited by L-NMMA only in arteries from adult pigs [EC50 (-logM): 8.9 ± 0.3 with indomethacin and 8.6 ± 0.3 with addition of L-NMMA]. These results suggest that hormonal changes associated with sexual maturity may affect post-transcriptional and/or translational regulation of eNOS protein resulting in lower plasma NO in adult male pigs. In addition, endothelium-derived inhibitory cyclooxygenase products seem to predominate in juveniles.
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