Inward Remodeling Follows Chronic Vasoconstriction in Isolated Resistance Arteries

Abstract

The hypothesis was tested that chronic vasoconstriction is followed by a structural reduction in lumen diameter, measured at full dilation. An in vitro model of pressurized rat skeletal muscle arterioles was used. During a 3-day experimental period, constriction of active vessels was achieved with fetal calf serum or endothelin-1 (ET-1). Maximal dilation revealed inward remodeling from 179 ± 6.5 µm lumen diameter on day 0 to 151 ± 6.3 µm on day 3 at 75 mm Hg in vessels incubated with serum (n = 8). Similarly, ET-1 induced inward remodeling from 182 ± 5.2 to 164 ± 3.7 µm (n = 6). When constriction during organoid culture was inhibited with papaverin or verapamil, inward remodeling was fully prevented: 184 ± 6.3 to 184 ± 5.8 µm for papaverin (n = 6) and 174 ± 5.5 to 177 ± 7.4 µm for verapamil (n = 6). A chronic reduction in diameter without tone was achieved in vessels that were kept at a low pressure (2–5 mm Hg; n = 6). Here, no remodeling was found, thereby ruling out that a chronic reduction in diameter alone is sufficient for inward remodeling. These data show that a persistent active reduction in lumen diameter is followed by inward remodeling of arterioles.

Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries

“…39 Finally, the rise in superoxide production in LF arteries might result from the initial macrophage infiltration after the decrease in blood flow. 40 As previously shown, 41 inward remodeling because of LF depends on the unopposed constrictor tone after the reduction in flow. Vasoconstrictor tone in RAs relies in large part on locally produced angiotensin II.…”

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two‐compartment in vitro set‐up

“…To be effective, such continuous vasodilation needs to be conducted to establish dilation over sufficient distance. Finally, sustained tone influences vascular remodelling, with deep tone being a drive for inward remodelling 23, 24. Previous modelling studies have shown that conducted responses, as important tone regulators, may play a role in vascular structural adaptations 13, 25.…”

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

“…Understanding the mechanisms which may modulate resistance arterial eutrophic remodelling is thus important, but these remain poorly understood. Prolonged vasoconstriction appears important, which, in itself may modulate re-organisation via the activities of cross-linking enzymes such as tissue-type transglutaminase and/ or integrins (Bakker et al, 2002(Bakker et al, , 2005Heerkens et al, 2006). It has been proposed that initial eutrophic remodelling may be an energetically favourable adaptive mechanism to normalise wall stress to maintain adequate blood flow, whilst a growth response, which may be observed in advanced or secondary hypertension, is related to a greater adverse prognosis (Izzard et al, 2006;Heagerty et al, 2010).…”

“…Whilst some studies suggest that structural changes follow a change in BP and/or prolonged arterial vasoconstriction (Bakker et al, 2002), there is evidence from studies using genetically modified mice that structural changes may precede the development of hypertension (Zacchigna et al, 2006). Whilst studies on isolated arteries from animal models of hypertension suggest that remodelling may be a consequence of reduced resistance arterial distensibility (at least in the cerebral circulation) (Izzard et al, 2006), others have shown increased distensibility (Laurant et al, 1997).…”

“…Whilst enhanced arterial constriction will, in itself, increase vascular resistance, it appears that the major consequence of altered levels of contractile activation in hypertension is on arterial remodelling. Studies on isolated rat small arteries maintained in culture have shown that chronic vasoconstriction itself induces eutrophic remodelling and that this remodelling is independent of the vasoconstrictor stimulus (Bakker et al, 2000(Bakker et al, , 2002(Bakker et al, , 2004. Furthermore, chronic in vivo infusion of vasoconstrictor stimuli in animals has also been shown to induce remodelling (Eftekhari et al, 2007).…”