Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries

Abstract

. Hypertension attenuates cell-tocell communication in hamster retractor muscle feed arteries. Am J Physiol Heart Circ Physiol 288: H861-H870, 2005. First published October 14, 2004 doi:10.1152/ajpheart.00729.2004.-This study examined whether hypertension attenuated cell-to-cell communication in skeletal muscle resistance arteries. Briefly, 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 application of vasoactive stimuli (via micropipette) to a small portion of a feed artery while diameter at sites distal to the point of agent application was monitored. In keeping with past observations, 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, conduction of endothelium-dependent vasodilation was attenuated in hypertensive hamsters. This decrease occurred in the absence of changes in vessel reactivity to intravascular pressure or to global application of phenylephrine, U-46619, or acetylcholine. We propose, on the basis of these physiological observations, quantitative mRNA measurements of connexins 37, 40, 43, and 45, and analysis of the literature, that an increase in endothelial-to-endothelial or smooth muscle-to-endothelial coupling resistance is likely responsible for hypertension-induced impairment in vascular communication. We hypothesize that this attenuation could contribute to the rise in total peripheral resistance characteristically observed in hypertension.

Vascular Gap Junctions in Hypertension

“…75,108 -112 Thus, conduction of vasomotor responses represents an attractive mechanism by which vascular gap junctions could participate in the control of arterial blood pressure. Consistent with this idea, conducted vasodilation is impaired in spontaneously hypertensive hamsters, 113,114 SHRs, 39,56 and Cx40 knockout animals. 59 It is worth noting that theoretical considerations suggest that gap junctional modulation of conduction of vasomotor signals may also play a role in the long-term control of peripheral resistance.…”

Intact Endothelium-Dependent Dilation and Conducted Responses in Resistance Vessels of Hypercholesterolemic Mice in vivo

“…Recently, this important endothelial function has been shown to be altered under pathological conditions. In chronically hypertensive animals, the conduction of dilations initiated by ACh was attenuated in vivo [32] as well as in isolated vessels [33]. Furthermore, it is well demonstrated that hypercholesterolemia alters the composition of Cx proteins in large conducting arteries in the area of plaque formation [28] but also in areas completely lacking signs of morphological changes [27].…”

Gap Junctions in the Control of Vascular Function

“…8). In support of the importance of coordination and integration of vasomotor tone in the control of arterial blood pressure (37, 55, 56) and structural adaptation of the microvascular network (152,153), conduction of vasodilator responses has been found to be impaired in spontaneously hypertensive hamsters (110,111) and SHRs (72).…”