Endothelial modulation of agonist-induced vasoconstriction in mesenteric microcirculation

Area of Science:

• Cardiovascular Physiology
• Endothelial Function
• Vascular Biology

Background:

• The vascular endothelium plays a crucial role in regulating vascular tone.
• Endothelium-derived relaxing factors (EDRF) are known to modulate vasoconstriction.
• The specific role of EDRF in the mesenteric circulation, a major vascular bed, requires further investigation.

Purpose of the Study:

• To investigate the role of the vascular endothelium in regulating methoxamine-induced vasoconstriction in rat mesenteric vascular beds.
• To examine age-related changes in endothelial modulation of vascular tone.

Main Methods:

• Isolated rat mesenteric vascular beds from young (8-week-old) and aged (16-week-old) rats were used.
• Methoxamine, an alpha(1)-adrenoceptor agonist, was perfused to induce vasoconstriction.
• Experiments involved intact endothelium, endothelium removal, and pharmacological inhibitors (e.g., nitric oxide synthase, cyclooxygenase, K(+)-channel inhibitors, gap junction inhibitor, thromboxane A(2) receptor antagonist, superoxide dismutase mimetic).

Main Results:

• In young rats, intact endothelium reduced methoxamine-induced vasoconstriction over time, independent of nitric oxide or cyclooxygenase pathways.
• This time-dependent reduction was abolished by endothelium removal, K(+)-channel inhibitors, and gap junction inhibitors, suggesting the involvement of endothelium-derived hyperpolarizing factor (EDHF).
• In aged rats, the time-dependent reduction of vasoconstriction was lost, and endothelium removal or specific inhibitors significantly increased vasoconstriction.

Conclusions:

• The vascular endothelium depresses methoxamine-induced vasoconstriction primarily through EDHF release.
• Ageing leads to the dysfunction of this endothelial-mediated vasodilation in the mesenteric circulation.
• These findings highlight age-related alterations in endothelial control of vascular tone.