Masters Theses

Julie A. Dunn

Date of Award

12-1987

Degree Type

Thesis

Degree Name

Master of Science

Major

Life Sciences

Major Professor

Roland M. Bagby

Committee Members

Hugh Welch

Abstract

The transition of the pulmonary circulation from fetal to newborn life is not fully understood. To characterize this process further, responses of third and fourth generation pulmonary arteries were assessed to the vasoconstrictors epinephrine, norepinephrine, serotonin and potassium chloride and the vasodilators nitroprusside, tolazoline, histamine and dopamine. Vessel segments were obtained from fetal and neonatal lambs at 7 days preterm and at 1, 7 and 21 days of age and mounted on a myograph to measure isometric tension. Responses to potassium chloride were measured as mg per mm2 of tissue (where mm2 = length x circumference). Responses to epinephrine, norepinephrine and serotonin were calculated as a percentage of the maximal KCl response. Responses to the vasodilators nitroprusside, tolazoline, histamine and dopamine were performed after a preconstricting dose of — s serotonin (10-5 M) had been administered. Percent dilation compared to serotonin constriction was calculated.

Fourth generation vessels were more responsive to KCl than third generation vessels. Additionally, the response of fourth generation vessels to KCl increased with age. No significant differences were noted to age for third generation vessels. Fourth generation vessels were significantly less responsive to epinephrine and norepinephrine than third generation vessels. Also, both generation vessels showed a significant decrease in sensitivity to these compounds at days 1 and 7 compared to preterm and 21 days of age. Serotonin was a potent vasoconstrictor in both third and fourth generation vessels, exceeding the maximal contractile response obtained to KCl. No differences were detected between generations to serotonin, however, like epinephrine and norepinephrine, sensitivity decreased at day 1 compared to 7 and 21 days.

No differences in maximum relaxation to nitroprusside and tolazoline among ages or between generations were demonstrated. Fourth generation vessels were more sensitive to tolazoline than third generation vessels. Nitroprusside was a substantially more potent vasodilator than tolazoline. Histaraine was a vasodilator in both third and fourth generation vessels at lower doses and a slight constrictor at higher doses in third generation vessels only. No differences were detected to age. Dopamine was a dilator in fourth generation vessels at 1 day of age. At high doses, a constrictor response was observed primarily of the third generation vessels.

Third generation vessels are functionally mature at birth as exhibited by their response to KCl. Fourth generation vessels are still undergoing maturation at birth through three weeks of age. The differential responses to both vasoconstrictors and vasodilators between age and generation are further evidence of the striking heterogeneity that exists in vascular smooth muscle both as a function of age and level of the pulmonary arterial tree. Furthermore, the decreased sensitivity of 1 and 7 day vessels to norepinephrine and epinephrine and of day 1 vessels to serotonin may be an important regulatory mechanism to ensure a drop in pulmonary vascular resistance necessary at birth for normal adaptation.

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