Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR

Abstract

Abstract-We examined the roles played by impaired K ϩ channels, diminished nitric oxide (NO) production, endothelin release, and smooth muscle membrane potential in the increased restenosis observed in spontaneously hypertensive rat (SHR) carotid arteries after angioplasty. The SHR carotid was found to be less polarized than that of normotensive Wistar rats (NWR), and it was further depolarized by the ␣ 2 agonist UK 14,304. This response was blocked by iberiotoxin, indicating that calcium-dependent K ϩ channels operate normally in the SHR carotid. Acetylcholine caused a hyperpolarization that was significantly smaller in SHR than in NWR carotids, indicating a deficient release of NO in the SHR. After angioplasty, SHR and NWR vessels were depolarized, returning to baseline after 10 days. In the SHR but not in the NWR the contralateral carotid was also depolarized, and this was prevented by the endothelin A/B receptor antagonist bosentan. After angioplasty, endothelin-1 plasma levels increased in both SHR and NWR, but the increase was significantly more prolonged in SHR. We found that the more pronounced restenosis observed in the SHR carotid after angioplasty is not due to impairment of calcium-dependent K ϩ channels but is related to the relatively depolarized vascular smooth muscles, involving endothelin release caused by reduced NO levels in that strain. Key Words: rats, spontaneously hypertensive Ⅲ angioplasty Ⅲ carotid arteries Ⅲ muscle smooth, vascular Ⅲ membranes Ⅲ endothelin T he vascular endothelium plays a role in blood flow control through the release of relaxant and contractile factors. Thus, to prevent overactivation of contractile responses, it releases relaxant factors such as endotheliumderived hyperpolarizing factor, prostanoids, and nitric oxide (NO). The endothelium also prevents the development of vascular lesions by inhibiting platelet aggregation, leukocyte adhesion, and proliferation of vascular smooth muscle cells. 1 This protective role is altered in pathological conditions such as arterial hypertension, which is characterized by cell permeability changes, leukocyte adhesion, and smooth muscle cell proliferation. Also, the repair mechanism designed to restore the vessel wall after damage from different causes frequently escapes self-limiting control, resulting in lumen narrowing caused by smooth muscle cell proliferation. These processes are the precursors of atherosclerotic plaque formation, which leads to increased vascular resistance and to restenosis. 2 Procedures such as atherectomy performed by balloon injury (angioplasty) widen the lumen but cause extensive endothelium destruction, leaving the vascular wall without protection. This injury stimulates medial smooth muscle cell proliferation and migration to the deendothelized surface to form a neointima. Neointima proliferation and subsequent vascular restenosis are believed to be the main events in the initiation of the atherosclerosis that limits the long-term efficacy of percutaneous transluminal coronary angioplasty. 3 It is well...

Impaired hemodynamics and endothelial vasomotor function via endoperoxide-mediated vasoconstriction in the carotid artery of spontaneously hypertensive rats

“…However, there have been no attempts to systematically investigate the mechanism responsible; notably, none have determined the effect of blocking calcium-activated K ϩ channels, which are ubiquitously involved in EDHF signaling (19). In SHR vasculature, peak VSM hyperpolarization (13) and ACh-stimulated EDHF-mediated relaxation are generally found to be impaired (17,19) but not in all cases (8,50), which may be related to age and/or the vascular wall remodeling state (17). Although our results might suggest that an EDHF may in fact be responsible for the augmented low [ACh]-stimulated SHR CCA relaxation, there are no additional data directly substantiating this supposition.…”

Endothelial dysfunction and restenosis following percutaneous coronary intervention

“…Endothelial cell dysfunction or removal following percutaneous coronary intervention may influence the long-term sequelae of this procedure. Specifically, the nitric oxide pathway is an important determinant of neointimal hyperplasia after experimental angioplasty [7,8]. Loss of coronary endothelial nitric oxide production has correlates with future risk of developing coronary artery lesions and of clinical coronary events [9].…”

Are flow-mediated vasodilatation and intima-media thickness of the brachial artery associated with restenosis after endovascular treatment of peripheral arterial occlusive disease?

“…Development of endovascular therapies during recent decades has enlarged the possible therapeutic strategies besides the traditional open surgical interventions [21]. Early results after angioplasty are superior to those for conservative treatment, but this is not proven for long-term results because of late restenosis in treated segments [22]. Because of the unfavourable long-term outcome of PTA versus medical treatment, especially in patients with claudication [23,24], it is important to identify those patients at high risk of restenosis, in order to take this risk into account for further treatment.…”

“…In experimental angioplasty the NO pathway seems to influence neointimal hyperplasia [22,26]. FMD is Table 3 Grade of stenosis and length of endovascular treated target lesions plus the association of these characteristics to restenosis after percutaneous revascularisation…”