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The Role of Phosphoramidon on the Biological Activity of
Big Endothelin-1 in the Rat Mesenteric Microcirculation in Vivo
Mohamed A. K. Abdelhalim
King Saud University, Faculty of Science, Department of Physics and Astronomy,
Biomedical Science Group, Riyadh, P.O. Box-2455, Riyadh 11 451, Saudi Arabia
E-mail: abdelhalimmak@yahoo.com: Phone: 009660509649633: Fax: 0096614673656
Abstract
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The goal of the present study was to clarify the role of metalloprotease
inhibitor phosphoramidon on the effects induced by big endothelin-1 (big ET-1)
in the rat mesenteric microcirculation in vivo, through investigating the
systemic blood pressure, diameter and blood flow velocity of arterioles and
venules of the rat mesentery. For this purpose, the rat mesentery was arranged
for in situ intravital microscopic observation under transillumination and
separate cumulative injections of big ET-1 and phosphoramidon were infused into
the right jugular vein, respectively. In these experiments twenty-five rats
(Charles River, 130 - 140 g) were used. The experiments were divided into two
groups. In the first group of experiments, cumulative injections of big ET-1
(1000-8000 pmole/kg) were infused through a catheter inserted into the right
jugular vein. Each dose of big ET-1 was infused 25 min prior to the infusion of
the following dose. Infusion of big ET-1 (1000-8000 pmole/kg) elicited a
long-lasting pressor effect. The infusion of low doses of big ET-1 (1000-2000
pmole/kg) elicited a significant (p < 0.05) dose-dependent increase in the
microvascular blood flow velocity both in arterioles (20 - 30 μm) and venules
(30 - 50 μm), and diameters of arterioles and venules exhibited a slight not
significant vasodilator effect. The infusion of high doses of big ET-1
(4000-8000 pmole/kg) elicited significant dose-dependant decrease in the blood
flow velocity of arterioles and venules, and diameters returned to the control
runs. This may be attributed to the gradual conversion of big ET-1 to ET-1, and
ET-1 is a potent vasoconstrictor. In the second group of experiments, cumulative
injections of phosphoramidon (30 mg/kg /10 min) were administered 10 min prior
to the infusion of big ET-1. These findings suggested that phosphoramidon
significantly suppressed long-lasting pressor effect, dose-dependent increase,
dose-dependent decrease and slow vasodilator effect produced by big ET-1 in the
rat mesenteric microcirculation, i.e., phosphoramidon markedly decreased the
activity of endothelin-converting enzymes (ECE), which converts big ET-1 to ET-1
in the rat mesenteric microcirculation.
Key words: Big endothelin-1; phosphoramidon (PR); blood flow velocity; rat
mesentery; microcirculation.
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