Prinzmetal angina-like events induced in isolated blood vessels and the role of calcium

Objective: Variant angina is also called Prinzmetal angina or vasospastic angina. In vivo, coronary arteries contract transiently or persistently and minimize the blood flow in the coronaries. Often, such a phenomenon is silent over months but suddenly reappears. Prinzmetal angina symptoms include chest pain episodes that happen, interestingly, during the night when the body is at rest. Since these episodes are transient, and testing may not show coronary artery disease, it is difficult to describe the mechanisms properly. Moreover, ideal medications for Prinzmetal angina treatment are difficult to determine. The vasoconstrictor activity of the blood vessel that induces the symptoms of Prinzmetal angina is clearly elevated, but it is unclear, if this is a pure smooth muscle effect via intracellular calcium elevation or if other structures are involved, like terminal nerve endings and exocytosis.
Materials and methods: The excised arteries were either perfused with saline or investigated in a wire myograph and exposed to standardized stimuli, i.e., electrical field stimulation (EFS), noradrenaline, and potassium-rich solution. This led to contractions due to transmitter release from perivascular varicosities. This was followed by specific inhibition of these contractions with the sodium channel blocker tetrodotoxin (TTX) and the L-type channel blocker nifedipine. Secondly, spontaneous phasic contractions were induced with the non-specific potassium channel inhibitor tetraethylammonium chloride (TEA). Contraction pattern over time, kinetics, and magnitude of single contractions in relation to standardized contractions along with sensitivity to TTX and nifedipine were investigated.
Results: Starting with perfused coronary arteries, we developed a model using rat mesenteric arteries in which the influence of the different factors on vascular contraction patterns could be studied. These factors include the excitability of smooth muscle and the nerve varicosities as well as the temporal excitation using EFS. In this study, we could clearly demonstrate that over-excitability can induce time-variant, periodic contractions, bursts of contractions, and, moreover, a sustained increase in tone. Such contractions increase the vascular perfusion resistance and reduce vascular flow.
Conclusion: We conclude that spontaneous phasic contractions of rat mesenteric arteries induced by TEA strongly depend on the function of the perivascular varicosities as well as calcium influx via Cav channels located in the smooth muscle wall and in the nerve varicosities. Most likely, spontaneous transmitter release from different varicosities leads to depolarization of directly affected smooth muscles, which is then propagated via the smooth muscle network. The simultaneous depolarization of a local muscular network results in a coordinated contraction and a reduced flow.