Biomedical subjects

Sandra R Severson

Publications and source records attributed to Sandra R Severson.

3 recordsLinked to original sources

PubMed2003

Effect of puberty on coronary arteries from female pigs.

Vascular function changes following loss of ovarian hormones in women at menopause and in experimental animals following surgical ovariectomy. Little is known about changes in vascular function during hormonal transition from sexual immaturity (juvenile) to sexual maturity. Therefore, experiments were designed to determine effects of natural puberty on vascular function in female pigs. Tissue was studied from eight juvenile (2-3 mo) and eight adult (5-6 mo) female pigs. Plasma nitric oxide (NO) was measured, and mRNA for endothelium-derived NO synthase (eNOS) and eNOS protein were determined in aortic endothelial cells. Rings of coronary arteries were suspended for measurement of isometric force in organ chambers. Serum 17beta-estradiol levels were comparable in the two groups, whereas the arithmetic mean of progesterone levels was about two-thirds lower in adults compared with juvenile pigs. Plasma NO was significantly higher in juveniles compared with adults, but mRNA and protein for eNOS were comparable. In coronary arteries, an alpha2-adrenergic agonist caused greater endothelium-dependent relaxations in rings from juvenile compared with adult pigs. Relaxations to bradykinin were similar in arteries from both groups, but inhibition of NO reduced relaxations only in arteries from juvenile pigs. Relaxations from NO were greater in arteries from adult compared with juvenile female pigs. In conclusion, coronary arterial endothelial and smooth muscle responses are selectively modulated at puberty in female pigs. At maturity, plasma NO is reduced and sensitivity of the smooth muscle to exogenous NO is increased. Posttranscriptional regulation of eNOS protein may explain differences in NO bioavailability in juvenile pigs.

Adrenergic alpha-Agonists↗

PubMed2003

Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs.

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 microM) than in adult (15.0 +/- 7.1 microM) 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 PGF2alpha, relaxations to an alpha2-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.

Animals↗

PubMed2002

Endothelial function in pigs transgenic for human complement regulating factor.

BACKGROUND: Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. Experiments were designed to characterize endothelial and smooth muscle function of arteries from pigs transgenic for hCD46. METHODS: Arterial blood from outbred pigs transgenic for hCD46 expression and nontransgenic animals of the same lineage was analyzed for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic endothelial cells were prepared for measurement of mRNA or activity for nitric oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were suspended in organ chambers for measurement of isometric tension. RESULTS: CNP was significantly greater, ACE was similar, and nitric oxide was significantly less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor activity of NOS differed between the groups. Endothelium-dependent relaxations to bradykinin and acetylcholine but not the calcium ionophore were shifted significantly to the left in femoral and pulmonary arteries from hCD46 transgenic pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did not inhibit relaxations in rings from transgenic pigs. CONCLUSIONS: Data suggest that expression of hCD46 on endothelium of pigs selectively augments endothelium-dependent relaxations to bradykinin by increased release of endothelium-derived factors other than nitric oxide. There does not seem to be any change in activity of ACE or NOS with expression of the human protein. Increased relaxations to bradykinin may be beneficial in lowering vascular resistance when transgenic organs are used for xenotransplantation.

Angiotensin I↗