Role of membrane potential and expression of endothelial factors in restenosis after angioplasty in SHR.
We examined the roles played by impaired K+ 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 alpha2 agonist UK 14,304. This response was blocked by iberiotoxin, indicating that calcium-dependent K+ 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+ channels but is related to the relatively depolarized vascular smooth muscles, involving endothelin release caused by reduced NO levels in that strain.
Dina
Janaina P
JP
Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.
Feres
Teresa
T
Paiva
Antonio C M
AC
Paiva
Therezinha B
TB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000800:Angioplasty, Balloon; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D000068438:Brimonidine Tartrate; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D006973:Hypertension / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D010455:Peptides; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D009569:Nitric Oxide; D000068438:Brimonidine Tartrate; C064719:iberiotoxin