Modulation of Myogenic Tone in Rat Mesenteric Resistance Arteries

Mary F. Keith, Philadelphia College of Osteopathic Medicine

Abstract

Myogenic tone is a component of autoregulation, and is the ability of vascular smooth muscle cells to respond to an increase in intraluminal pressure with a vasoconstriction. There is controversy over the presence of myogenic tone in mesenteric resistance arteries. There are also conflicting results regarding the effects of acute high glucose, protein kinase C (PKC) inhibition, and cyclooxygenase inhibition on myogenic tone in general. This study aimed to determine if myogenic tone is present in mesenteric resistance arteries and, in addition, to determine the modulation effects, if any, of acute high glucose (25 mM), chelerythrine, a nonspecific PKC inhibitor, and indomethacin, a cyclooxygenase inhibitor, on the microvessels. Tertiary branches of the mesenteric artery were isolated from male Sprague Dawley rats and pressurized in an arteriograph chamber. The vessel preparation was deemed to possess endothelium due to a significant vasodilation after application of acetylcholine to phenylephrine pre-constricted vessels. Mesenteric resistance arteries exhibited a decrease in diameter in response to an increase in intraluminal pressure in a calcium solution (1.8 mM). They had significantly larger vessel diameters when exposed to calcium-free solution at 60, 75, 90, and 105 mmHg when compared to diameters in a calcium solution (1.8 mM) indicating the presence of myogenic tone in a calcium solution (1.8 mM). Mesenteric resistance vessels exposed to acute high glucose (25 mM) exhibited a significant increase in vessel diameter at 75, 90, and 105 mmHg compared to vessels exposed to normal glucose (5.5 mM). Inhibition of PKC under acute high glucose conditions resulted in a significant decrease in vessel diameter at 30,45, and 60 mmHg when compared to high glucose conditions and a significant decrease in vessel diameter at 5, 30, and 45 mmHg when compared to normal glucose conditions. Tone in the presence of high glucose was not altered by PKC inhibition at 75, 90, and 105 mmHg. Vessels exposed to acute high glucose for 20 minutes exhibited an initial transient vasodilation and a subsequent decrease in vessel diameter, the latter of which was completely reversed by indomethacin. To our knowledge, this is the first study to describe this pattern of myogenic response to acute high glucose, PKC inhibition, and cyclooxygenase inhibition in mesenteric resistance vessels.