Abstract
dc:description.abstract<p>To determine the developmental changes in myocardial α<sub>1</sub>-adrenergic receptor system, we employed [<sup>3</sup>H-Prazosin] binding technique to characterize α<sub>1</sub>-adrenergic receptors in both fetal and adult sheep myocardial ventricular membrane preparations. Myocardial α<sub>1</sub>-adrenergic receptor density (Bmax) declined during developmental process with both fetal left ventricle(LV) and fetal right ventricle(RV) having significantly more binding sites than respective adult ventricles. We also demonstrated that the positive inotropic response to the α<sub>1</sub>-adrenergic agonist phenylephrine did not differ significantly between the fetal and adult ventricles.</p> <p>The present study also investigated the effect of long-term high-altitude hypoxemia on the α<sub>1</sub>- and β<sub>1</sub>-adrenergic receptor interaction in the heart. The interactions between two receptor systems were examined by prior stimulation of muscles with α<sub>1</sub>-adrenergic agonist phenylephrine (PHE). Hypoxic left ventricle without prior phenylephrine stimulation produced greater response to isoproterenol stimulation {maximal tension developed (Tmax, g/mm<sup>2</sup> =: 1.16 ± 0.18)}; than normoxic left ventricle without prior phenylephrine stimulation {maximal tension developed (Tmax, g/mm<sup>2</sup> =: 0.41 ± 0.05)} (p<0.01). Mycocardial α<sub>1</sub>- and β<sub>1</sub>-adrenergic antagonistic interaction was observed only in hypoxic LV. In conclusion, chronic hypoxemia augmented isoproterenol dose-responses in hypoxic left ventricle. Phenylephrine antagonized effects of isoproterenol in hypoxic left ventricle indicating an α<sub>1</sub>- and β<sub>1</sub>-adrenergic interaction during long-term high-altitude hypoxemia. </p> <p>To determine the effects of long-term high-altitude hypoxemia on myocardial α<sub>1</sub>-adrenergic receptor system and Ins(1,4,5)P<sub>3</sub> (IP<sub>3</sub>) responses, we employed [<sup>3</sup>H-Prazosin] binding technique and Ins(1,4,5)P<sub>3</sub> assay to characterize α<sub>1</sub>-adrenergic receptors and Ins( 1,4,5)P<sub>3</sub> in the sheep myocardial preparations. Long-term high-altitude hypoxemia significantly depressed myocardial α<sub>1</sub>-adrenergic receptor density (Bmax in fmol/mg) in fetal right ventricle (RV). In contrast, it did not affect the dissociation constant (Kd). Long-term hypoxemia also significantly decreased Ins(1,4,5)P<sub>3</sub> production in response to phenylephrine stimulation in the fetal right ventricle. In conclusion, myocardial α<sub>1</sub>-adrenergic receptor density and Ins(1,4,5)P<sub>3</sub> production in response to agonist stimulation in the fetal right ventricle were decreased as result of long-term high-altitude hypoxemia.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation
- Discipline thesis:degree_discipline
- Pharmacology
- Year
- 1997
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Chen, Bihong T.
- Contributors dc:contributor
-
- Raymond D. Gilbert
- Ian Fraser
- Ramon G. Gonzalez Jr.
- Lawrence D. Longo
- William J. Pearce
Subjects
dc:subject × 2Rights
dc:rights- Statement dc:rights
-
- This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
- Language dc:language
- English
Identifiers
dc:identifier.*- Repository record dc:identifier
- https://scholarsrepository.llu.edu/etd/1320
- OAI identifier oai:identifier
- oai:scholarsrepository.llu.edu:etd-2101