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Am J Physiol Heart Circ Physiol 285: H1168-H1176, 2003. First published May 8, 2003; doi:10.1152/ajpheart.00029.2003
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Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs

Ritu Chatrath,1 Karen L. Ronningen,2 Sandra R. Severson,2 Peter LaBreche,2 Muthuvel Jayachandran,2 Margarita P. Bracamonte,3 and Virginia M. Miller2,3

1Division of Pediatric Cardiology and Departments of 2Surgery and 3Physiology and Biophysics, Mayo Clinic Rochester, Rochester, Minnesota 55905

Submitted 8 April 2003 ; accepted in final form 1 May 2003

In humans, 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 (NO) and coronary arterial responses during puberty. Plasma was collected from juvenile (2–3 mo of age) and adult (5–6 mo of age) male pigs (n = 8/group) for measurement of NO, and aortic endothelial cells were collected for measurement of mRNA and protein for endothelial NO synthase (eNOS). Although plasma NO was higher in juvenile (67.0 ± 25.6 µM) than in adult (15.0 ± 7.1 µM) male pigs, eNOS protein was similar in both groups. However, levels of mRNA for eNOS were 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 PGF2{alpha}, relaxations to an {alpha}2-adrenergic agonist were significantly inhibited by indomethacin only in juvenile pigs [EC50 (–log M), 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 (–log M), 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 posttranscriptional and/or translational regulation of eNOS protein and result in lower plasma NO in adult male pigs. In addition, endothelium-derived inhibitory cyclooxygenase products seem to predominate in juveniles.

cyclooxygenase; estrogen; testosterone; nitric oxide; prostacyclin


Address for reprint requests and other correspondence: V. M. Miller, Dept. of Surgery and Physiology and Biophysics, Mayo Clinic Rochester, 200 First St. S.W., Rochester, MN 55905 (E-mail: miller.virginia{at}mayo.edu).






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