Effect of chronic denervation on pharmacological responsiveness of coronary vessels

We have hypothesized that the well-established regional heterogeneity of the properties of the vascular smooth muscle results from peculiarities of the microenvironment in every region. In particular, the coronary vasculature has well-established differences between large and small coronary arteries in their responsiveness to alpha and beta agonists, nitroglycerin and adenosine. To test our hypothesis, we altered the micro-environment of coronary vessels by chronic surgical sympathectomy in dogs. Our in vitro studies on vessels from normally innervated hearts confirmed previous studies and showed that in large vessels, alpha and beta epinephrine or norepinephrine responses can be demonstrated; the alpha effect is dominant and epinephrine is a more potent alpha agonist than is norepinephrine. In small vessels only a beta catecholamine effect can be demonstrated. Chronically sympathectomized blood vessels show an alpha norepinephrine effect in small vessels. Denervation caused a reduction in the sensitivity to K+-induced contraction in both large and small vessels. In large vessels the responses to nitroglycerin were not affected by denervation, whereas in small vessels the sensitivity to adenosine was reduced. These results indicate that chronic denervation alters the pharmacological responsiveness of the vasculature to various agonists indicating that vascular smooth muscle possesses the ability to respond to long-term modulatory influences arising in the immediate environment.