Abstract

To determine the developmental changes in myocardial α1-adrenergic receptor system, we employed [3H-Prazosin] binding technique to characterize α1-adrenergic receptors in both fetal and adult sheep myocardial ventricular membrane preparations. Myocardial α1-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 α1-adrenergic agonist phenylephrine did not differ significantly between the fetal and adult ventricles.

The present study also investigated the effect of long-term high-altitude hypoxemia on the α1- and β1-adrenergic receptor interaction in the heart. The interactions between two receptor systems were examined by prior stimulation of muscles with α1-adrenergic agonist phenylephrine (PHE). Hypoxic left ventricle without prior phenylephrine stimulation produced greater response to isoproterenol stimulation {maximal tension developed (Tmax, g/mm2 =: 1.16 ± 0.18)}; than normoxic left ventricle without prior phenylephrine stimulation {maximal tension developed (Tmax, g/mm2 =: 0.41 ± 0.05)} (p<0.01). Mycocardial α1- and β1-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 α1- and β1-adrenergic interaction during long-term high-altitude hypoxemia.

To determine the effects of long-term high-altitude hypoxemia on myocardial α1-adrenergic receptor system and Ins(1,4,5)P3 (IP3) responses, we employed [3H-Prazosin] binding technique and Ins(1,4,5)P3 assay to characterize α1-adrenergic receptors and Ins( 1,4,5)P3 in the sheep myocardial preparations. Long-term high-altitude hypoxemia significantly depressed myocardial α1-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)P3 production in response to phenylephrine stimulation in the fetal right ventricle. In conclusion, myocardial α1-adrenergic receptor density and Ins(1,4,5)P3 production in response to agonist stimulation in the fetal right ventricle were decreased as result of long-term high-altitude hypoxemia.

LLU Discipline

Pharmacology

Department

Pharmacology

School

Graduate School

First Advisor

Raymond D. Gilbert

Second Advisor

Ian Fraser

Third Advisor

Ramon G. Gonzalez Jr.

Fourth Advisor

Lawrence D. Longo

Fifth Advisor

William J. Pearce

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1997

Date (Title Page)

6-1997

Language

English

Library of Congress/MESH Subject Headings

Anoxia -- physiopathology; Heart -- physiopatholog; . Receptors, Adrenergic, Alpha-1.

Type

Dissertation

Page Count

vii; 85

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage 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.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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