This study examined whether hypertension attenuated cell-to-cell communication in skeletal muscle resistance arteries. In brief, arteries feeding the retractor muscle of normotensive and hypertensive hamsters were cannulated, pressurized and superfused with a physiological saline solution. Cell-to-cell communication was functionally assessed by applying vasoactive stimuli (via micropipette) to a small portion of a feed artery while monitoring diameter at sites distal to the point of agent application. In keeping with past observations, the discrete application of a smooth muscle depolarizing agent (phenylephrine or KCl) elicited a localized vasoconstriction that conducted poorly along feed arteries from normotensive hamsters. In contrast, acetylcholine, an agent known to hyperpolarize endothelial cells, elicited a vasodilation in normotensive feed arteries that conducted with little decay. Whereas smooth muscle depolarizing agents continued to elicit a localized response, the conduction of endothelial-dependent vasodilation was attenuated in hypertensive hamsters. This decrease occurred in the absence of changes in vessel reactivity to intravascular pressure or to the global application of phenylephrine, U46619 or acetylcholine. We propose, based on these physiological observations, quantitative mRNA measurements of connexin 37, 40, 43 and 45, and an analysis of the existing literature, that an increase in endothelial-to-endothelial or smooth muscle-to-endothelial coupling resistance is likely responsible for the hypertension-induced impairment in vascular communication. We hypothesize that this attenuation could contribute to the rise in total peripheral resistance characteristically observed in hypertension.