Title

Mechanism Involved in Testosterone Modulation of Myogenic Tone in Microvessels of the Rat Mesenteric Arterial Bed

Date of Award

5-2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Mary P Owen, PhD, JD

Second Advisor

Richard E White, PhD

Third Advisor

Shu Zhu, MD, PhD

Fourth Advisor

Brian M Matayoshi, PhD

Abstract

Myogenic tone is the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. It is a component of autoregulation and is thought to be more important in resistance microvessels than in larger vessels. There is a paucity of studies investigating the ability of testosterone (TES) to modulate myogenic tone in the resistance vasculature and even fewer evaluating this phenomenon at physiological concentrations of TES. Tertiary branches of the mesenteric artery were isolated from male Sprague Dawley rats and then mounted and pressurized in an arteriograph chamber (Living Systems Instrumentation, St. Albans, Vermont). Myogenic tone was established in these resistance microvessels. In vessels with myogenic tone, acetylcholine (70 µM) produced a significant increase in the mesenteric resistance vessels' diameter verifying the presence of a functional endothelium (Furchgott and Zawadzki, 1980) in this preparation. A decrease in diameter at 60, 75, 90, and 105 mmHg in these vessels when placed in HEPES physiological solution with calcium ( 1.8 mM), compared to a significant increase in diameter in the vessels at these same pressures when placed in HEPES calcium-free solution and EGTA (2mM), demonstrated that myogenic tone in these mesenteric resistance vessels is dependent on calcium. Following the development of myogenic tone at 75 mmHg, TES (20 nM) was added to the chamber bath and diameter and wall thickness measurements were recorded at 0 and 5 minutes. These mesenteric resistance vessels exhibited an increase in diameter at this nanomolar concentration indicating that TES has a vasodilation effect on myogenic tone in tertiary branches of the mesenteric artery at physiological concentrations. When Nω-nitro-L-arginine methyl ester (L-NAME) (10 µM), a nitric oxide synthase (NOS) inhibitor, was added to the arteriograph chamber following the addition of TES, the diameter of the vessel decreased. L-NAME totally reversed the TES-induced vasodilation effect on myogenic tone. In addition, L-NAME caused an increase in myogenic tone itself suggesting that myogenic tone itself is modulated (decreased) by nitric oxide (NO). To our knowledge, this is the first in vitro study to show a complete reversal of TES's vasodilation effect on myogenic tone by L-NAME in a systemic microvessel. This finding suggests that the TES-induced vasodilation of myogenic tone is completely NO dependent in these resistance micro vessels of the mesenteric vascular bed.

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