RESUMO
To investigate lisinopril effect on the contribution of nitric oxide (NO) and K(Ca) channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensive WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K(Ca) channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SK(Ca) and IK(Ca) channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SK(Ca) and BK(Ca) proteins. Lisinopril treatment increased expression of eNOS, SK(Ca), BK(Ca) channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SK(Ca) and IK(Ca) channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SK(Ca) and IK(Ca) channels is reduced.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Lisinopril/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Canais de Potássio Cálcio-Ativados/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Cálcio-Ativados/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismoRESUMO
AIMS: This study examined the long-term effects of nitrous oxide anaesthesia on serum levels of cobalamin and folate, red cell folate levels and haematological parameters, and neurological status in elderly Omani patients. METHODS: Sixty-nine consecutive patients undergoing ophthalmic surgery were randomly and double-blind assigned to nitrous oxide or propofol anaesthesia. They met the following entry criteria: age 55 years or above, no major organ failure, no clinical signs or symptoms of cobalamin or folate deficiency, mean cell volume (MCV)
