Endothelial and myogenic regulation of coronary artery tone in the mouse

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Vascular Biology

Background:

• Coronary arteries play a crucial role in regulating blood flow to the heart.
• Understanding the mechanisms of coronary vasomotor tone is essential for treating cardiovascular diseases.
• Murine models are frequently used to study human cardiovascular conditions, but species-specific differences must be considered.

Purpose of the Study:

• To characterize the myogenic tone and vasomotor responses of isolated mouse septal coronary arteries.
• To investigate the roles of endothelin receptors, adrenergic receptors, and nitric oxide in regulating mouse coronary vascular tone.
• To compare murine coronary artery responses with those reported in other species, particularly rats and humans.

Main Methods:

• Isolation and mounting of mouse ventricular septal arteries (150-200 microm) on a pressure myograph.
• Assessment of spontaneous myogenic tone at 70 mm Hg.
• Pharmacological manipulation using endothelin receptor antagonists (bosentan), alpha- and beta-adrenergic agonists and antagonists, and nitric oxide synthase inhibitors (N(omega)-nitro-L-arginine methyl ester).

Main Results:

• Mouse septal arteries developed significant spontaneous myogenic tone, exceeding that of rat septal arteries.
• Endothelin ET(A) and ET(B) receptor inhibition reduced basal tone, indicating endothelin's role in tone development.
• Alpha(2)-adrenoceptor agonists (BHT 920, clonidine) and noradrenaline induced concentration-dependent vasodilatation, mediated by endothelial alpha(2)-adrenoceptors.
• Acetylcholine-induced vasodilatation was endothelium-dependent and nitric oxide synthase-dependent.
• Bradykinin and substance P did not elicit vasomotor effects, suggesting differences from other species.

Conclusions:

• Mouse coronary arteries possess substantial myogenic tone and unique adrenergic receptor-mediated vasomotor responses.
• Endothelin, alpha(2)-adrenoceptors, and nitric oxide signaling are key modulators of mouse coronary vascular tone.
• Significant differences in vasomotor responses between mouse and human coronary arteries may limit the direct translatability of mouse models for certain human coronary vessel diseases.