Abstract
AMP‐activated protein kinase (AMPK) is emerging as an important regulator of vascular function and has differential effects on vascular tone in arteries from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The current study aims to determine: if AMPK modulates the vasocontraction response to phenylephrine (PE); if AMPK effects are mediated by a downstream ROCK effect; and, if hypertension alters the regulatory effects of AMPK. Isolated common carotid artery (CCA) segments (denuded of endothelium) from WKY and SHR were used to determine vasomotor dose‐responses to PE (10−8–10−4 M) after control (CON) incubation, or incubation with: AMPK inhibitor Compound C (CC; 20 μM); ROCK inhibitor Y26732 (1 μM); or, CC+Y26732. PE contraction was suppressed in SHR vs WKY CON (EC50 55±6 vs 17 ± 4 nM, P <0.05). CC or Y26732 each suppressed PE contraction (increased EC50 vs respective CON) in CCA of each of WKY and SHR. The CC + Y26732 effect was greater than either individual drug effect in both WKY and SHR, but was not completely additive. While the absolute values of EC50 were higher in SHR vs WKY for each condition, the effects of CC and Y26732 on PE EC50 were relatively (to respective CON) greater in WKY vs SHR. Results suggest that AMPK may contribute to modulating PE contraction in denuded CCA via Rock‐dependent and –independent mechanisms, and that hypertension suppresses this effect of AMPK. Supported by NSERC
Published Version
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