Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2

1 We investigated the response to pressure (myogenic tone) and flow of rat mesenteric resistance arteries cannulated in an arteriograph which allowed the measurement of intraluminal diameter for controlled pressures and flows. Rats were treated for 3 weeks with N-G-nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) or L-NAME plus the angiotensin I converting enzyme inhibitor (ACEI) quinapril (10 mg kg(-1) day(-1)). 2 Mean blood pressure increased significantly in chronic L-NAME-treated rats (155+/-4 mmHg, n=8, vs control 121+/-6 mmHg, n=10; P<0.05). L-NAME-treated rats excreted significantly more dinor-6-keto prostaglandin F-1 alpha (dinor-6-keto PGF(1 alpha)), the stable urinary metabolite of prostacyclin, than control rats. The ACEI prevented the rise in blood pressure and the rise in urinary dinor-6-keto PGF(1 alpha) due to L-NAME. 3 Isolated mesenteric resistance arteries, developed myogenic tone in response to stepwise increases in pressure (42+/-6 to 847+/-10 mN mm(-1), from 25 to 150 mmHg, n=9). Myogenic tone was not significantly affected by the chronic treatment with L-NAME or L-NAME + ACEI. 4 Flow (100 mu l min(-1)) significantly attenuated myogenic tone by 50+/-6% at 150 mmHg (n=10). Flow-induced dilatation was significantly attenuated by chronic L-NAME to 22+/-6% at 150 mmHg (n=10, P=0.0001) and was not affected in the L-NAME + ACEI group. 5 Acute in vitro N-G-nitro-L-arginine (L-NOARG, 10 mu M) significantly decreased flow-induced dilatation in control but not in L-NAME or L-NAME + ACEI rats. Both acute indomethacin (10 mu M) and acute NS 398 (cyclo-oxygenase-2 (COX-2) inhibitor, 1 mu M) did not change significantly how-induced dilatation in controls but they both decreased flow-induced dilatation in the L-NAME and L-NAME + ACEI groups. Acute Hoe 140 (bradykinin receptor inhibitor, 1 mu M) induced a significant contraction of the isolated mesenteric arteries which was the same in the 3 groups. 6 Immunofluorescence analysis of COX-2 showed that the enzyme was expressed in resistance mesenteric arteries in L-NAME and L-NAME + ACEI groups but not in control. COX-1 expression was identical in all 3 groups. 7 We conclude that chronic inhibition of nitric oxide synthesis is associated with a decreased flow-induced dilatation in resistance mesenteric arteries which was compensated by an overproduction of vasodilator prostaglandins resulting in part from COX-2 expression. The decrease in flow-induced dilatation was prevented by the ACEI, quinapril.