Comparison of Vascular Reactivity Profiles in the Superior Mesenteric Artery and Aorta of Normal and Insulin Resistant Wistar Rats: Role of Cyclooxygenase

Abstract

Regulation of vascular tone in the superior mesenteric artery (SMA) is an important contributor to elevating blood pressure secondary to insulin resistance. Although narrower than the aorta, it is debatable whether the SMA is a conduit or resistance vessel. In fructose-fed rats, an animal model of the metabolic syndrome, the contribution of cyclooxygenase (COX) isoforms to vascular reactivity in both aorta and SMA is unclear. We evaluated and compared the effects of COX-1 and 2 on (PE) phenylephrine-evoked contraction in the aorta and SMA of 9-week fructose-fed male rats. Following induction of insulin resistance and increased systolic blood pressure, isolated aorta and SMA rings were incubated with a selective COX-2 inhibitor NS-398 (10−6M) and non-selective inhibitor indomethacin (10−5M). Responses to PE (10−9 – 10−4M) were obtained prior to and after treatment. We also studied the changes in relaxation to ACh in SMA in the presence of indomethacin. Contraction to PE was reduced in both the aorta and SMA of fructose-fed rats in presence of either NS-398 or indomethacin as compared to untreated rings. Conversely, inhibition of COX also improved endothelium- dependent relaxation in the SMA of fructose-fed rats suggesting a proconstrictor role for COX-2-catalyzed prostanoids. In conclusion our results point to a conduit role for the SMA in vasoconstriction, which is similar to that observed in the aorta.