Activation of AMP‐activated protein kinase (AMPK) causes vasorelaxation in isolated mesenteric arteries of hypertensive and normotensive rats

Previous studies have shown that AMPK activation causes relaxation in isolated vessels from healthy animals but this has not been investigated in dysfunctional resistance arteries of hypertensive animals. Here we investigate the effects of AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) on resistance arteries from normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR). Mesenteric arteries were mounted on a small vessel myograph, pre‐contracted with 10−5M norepinephrine and exposed to increasing concentrations of AICAR (10−6, 10−4, 10−2M). Dose‐dependent relaxation occurred (~10% at 10−6M and ~90% at 10−2M [AICAR], respectively), and did not differ between SHR and WKY. Incubation with the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 10−4M) blunted relaxation in the WKY at 10−6M AICAR (by ~17% vs. CON, n=6, P<0.01), but did not affect relaxation at higher [AICAR]. Conversely, L‐NAME significantly blunted the relaxation response of SHR rings across all [AICAR] (by ~15–25% vs. CON, n=8, all P<0.01). Thus AICAR causes relaxation in both SHR and WKY mesenteric artery segments, but the relaxation response to AICAR is more NO‐dependent in vessels from SHR compared to WKY. Collectively these findings suggest that AMPK could influence the regulation of resistance vasculature in normotensive and hypertensive animals in an NO‐dependent manner.

Activation of AMP‐activated protein kinase (AMPK) causes vasorelaxation in isolated mesenteric arteries of hypertensive and normotensive rats Journal Articles