Acute Myocardial Ischemia Alters Vascular Reactivity of Tertiary Mesenteric Arteries

Abstract

Ischemia produces a reduction in vascular tone and the sensitivity to NO mediated vasodilatation of the ischemic vascular bed. However, whether cardiac ischemia has any deleterious effect on the contractile properties of nonischemic, peripheral vascular beds is unknown. Thus, the aim of the current study was to determine whether acute myocardial ischemia results in peripheral vascular dysfunction. We determined force and the sensitivity to ACh mediated smooth muscle relaxation of tertiary (3rd) mesenteric arteries of rats following 30 min of myocardial ischemia (ischemia) compared to sham (perfused). During KCl depolarization, myocardial ischemia did not affect peak force, but significantly depressed force maintenance. For perfused vessels, KCl depolarization resulted in a significant increase in both smooth muscle (SM) and nonmuscle (NM) light chain (LC) phosphorylation. However, in ischemic vessels, there was not only a decrease in the expression of the LCs, but also SM-LC phosphorylation was depressed whilst there was no detectable NM-LC phosphorylation. Compared to perfused vessels, there was a decrease in the relaxation in response to both ACh and 8-Br-cGMP in ischemic 3rd mesenteric arteries, and in the expression of MYPT1. Further, ischemia was associated with an increase in protein poly-ubiquitination, suggesting that during ischemia both the LCs and MYPT1 are targeted for degradation by the proteasome. These results suggest that NM myosin contributes to the contractile properties of 3rd mesenteric vessels, and ischemia inhibits NM myosin to depress vascular tone. Additionally, ischemia results in a decrease in MYPT1 expression, which contributes to the decrease in the sensitivity to NO mediated vasodilatation. In conclusion, acute myocardial ischemia alters the peripheral vascular phenotype, which contributes to the decrease in both force maintenance and the sensitivity to NO mediated smooth muscle relaxation.