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...