Endothelium-associated vasodilators in rat skeletal muscle microcirculation

Area of Science:

• Cardiovascular Physiology
• Microcirculation Research
• Pharmacology

Background:

• Endothelium-derived relaxing factor (EDRF) is crucial for regulating vascular tone.
• The role of EDRF in microvascular responses to various agents requires further investigation.

Purpose of the Study:

• To investigate the involvement of guanosine 3',5'-cyclic monophosphate (cGMP)-associated EDRF in mediating microvascular responses in vivo.
• To determine the influence of specific pharmacological agents on arteriolar diameter in response to endogenous and exogenous stimuli.

Main Methods:

• In vivo microscopic observation and quantification of cremaster muscle arteriole diameter changes in pentobarbital-anesthetized rats.
• Topical application of various agents including acetylcholine, bradykinin, ATP, adenosine, histamine, prostaglandin E2, norepinephrine, and calcium ionophore A23187.
• Pharmacological manipulation using hydroquinone, methylene blue, indomethacin, and superoxide dismutase to probe EDRF pathways.

Main Results:

• Hydroquinone and methylene blue inhibited acetylcholine-, bradykinin-, and ATP-induced vasodilation, but not responses to adenosine, histamine, or prostaglandin E2.
• These inhibitions were reversed by superoxide dismutase, indicating superoxide anion antagonism.
• Constrictor responses to norepinephrine were unaffected by hydroquinone or methylene blue.
• Unlike in larger vessels, vasodilator responses to A23187 or arachidonic acid were blocked by cyclooxygenase inhibition.

Conclusions:

• EDRF likely contributes to the control of microvascular tone.
• Superoxide anions may antagonize EDRF-mediated vasodilation in arterioles.
• Stimuli eliciting EDRF-mediated dilation differ between small and large blood vessels.