Cellular Mechanisms Underlying Myogenic Reactivity in Isolated Arterioles

<p>The myogenic reactivity provides one of the principal mechanisms for blood flow autoregulation. The aims of the performed studies described in this dissertation were to test the role of [Ca²⁺]_i and MLC phosphorylation in arteriolar myogenic reactivity and further examine the source(s) of activator Ca²⁺ required to initiate and maintain myogenic vasoconstriction. In addition, the possible underlying mechanism of contractile protein expression was also addressed.</p> <p>These studies used male Sprague Dawley rats of 200 ~ 350 grams body weight. Experiments were carried out using rat cremaster first order arterioles and mesenteric vessels. Gel electrophoresis and immunoblotting techniques were employed to analyze and identify the contractile protein isoforms and myosin light chain phosphorylation while the functional aspects of the studies were performed on isolated cannulated vessel preparations. Intracellular calcium was measured using a video based image system with fura-2 as a fluorescent Ca²⁺ indicator. A fluorescence image intensity ratio of 340nm over 380nm excitation wavelengths was accepted as a measurement of [Ca²⁺]ⁱ. Samples for measuring MLC phosphorylation were collected by quickly freezing the vessels at the desired time points after different treatments according to the computerized image analysis system.</p> <p>The following conclusions were drawn from the studies presented in this dissertation: 1) Myogenic reactivity may, in part, relate to differences in structural composition of contractile proteins; 2) [Ca²⁺]_i and MLC phosphorylation play obligatory roles in the setting of arteriolar spontaneous tone and myogenic reactivity; 3) Wall tension appears to be the detected variable and a regulatory factor during the arteriolar myogenic reactivity; 4) α-adrenergic agonist induced-arteriolar contraction also depends on increases in [Ca²⁺]_i and MLC phosphorylation, however, signaling pathways appear to differ from that described for myogenic contraction. Further, mechanisms involving the contractile element Ca²⁺ sensitization also contribute to the agonist-induced response; 5) The extracellular Ca²⁺ source is most important in the maintenance of arteriolar basal tone and the myogenic contraction. While Ca²⁺ entry from the extracellular environment, largely via VOCs, is a mandatory process, Ca²⁺ release from intracellular stores may also be involved in the myogenic constriction. An additional Ca²⁺ entry mechanism, possibly receptor-operated Ca²⁺ channels, is involved in the agonist-induced contractions.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Year dc:date.available

1995

Author dc:creator

• Zou, Hui

Contributors dc:contributor

• Michael A. Hill
• Stephen J. Beebe
• Peter F. Blackmore
• Barbara Hargrave
• Paul H. Ratz

• Blood flow
• Calcium
• Phosphorylation
• Anatomy
• Animal Structures
• Cell Biology
• Physiology

Repository record dc:identifier

https://digitalcommons.odu.edu/biomedicalsciences_etds/90

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biomedicalsciences_etds-1100