RESUMO
OBJECTIVES: To determine whether secondhand smoke (SHS) induces pulmonary artery endothelial dysfunction, and whether dietary L-arginine supplementation is preventive. BACKGROUND: SHS causes coronary and peripheral arterial endothelial dysfunction. METHODS: The effects of L-arginine supplementation (2.25% solution) and SHS (10 weeks) on pulmonary vascular reactivity were examined in 32 rabbits fed a normal diet. Endothelium-dependent relaxation of precontracted pulmonary artery segments was studied using acetylcholine and calcium ionophore. Endothelium-independent relaxation was studied using nitroglycerin. Endothelial and serum L-arginine levels were measured by chromatography. In eight SHS-exposed and in eight control rats, pulmonary artery nitric oxide synthase (NOS) activity and arginase activity were studied using the titrated arginine to citrulline conversion assay. RESULTS: SHS reduced maximal acetylcholine-induced (p = 0.04) and calcium ionophore-induced (p = 0.02) relaxation. L-Arginine increased maximal acetylcholine-induced (p = 0.047) vasodilation. SHS and L-arginine did not influence nitroglycerin-induced relaxation. SHS reduced endothelial L-arginine (p = 0.04) but not serum L-arginine. L-Arginine supplementation increased endothelial (p = 0.007) and serum L-arginine (p < 0.0005). Endothelium-dependent relaxation induced by acetylcholine and calcium ionophore varied directly with endothelial (r = 0.67, r = 0.67) and serum L-arginine (r = 0.43, r = 0.45), respectively. SHS reduced constitutive NOS activity (p = 0.03). CONCLUSIONS: SHS reduces pulmonary artery endothelium-dependent relaxation by decreasing NOS activity and possibly by decreasing endothelial arginine content. L-Arginine supplementation increases serum and endothelial L-arginine stores and prevents SHS-induced endothelial dysfunction. L-Arginine may offset the deleterious effect of SHS on pulmonary arteries by substrate loading of the nitric oxide pathway.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Vasodilatação/efeitos dos fármacos , Animais , Arginase/metabolismo , Arginina/farmacologia , Feminino , Óxido Nítrico Sintase/metabolismo , Nitroglicerina/farmacologia , RatosAssuntos
População Negra , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Educação em Saúde/organização & administração , Promoção da Saúde/organização & administração , Negro ou Afro-Americano/estatística & dados numéricos , Distribuição por Idade , Idoso , Cardiologia , Doenças Cardiovasculares/epidemiologia , Indústria Farmacêutica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Apoio à Pesquisa como Assunto , Fatores de Risco , Distribuição por Sexo , Sociedades Médicas , Estados Unidos/epidemiologia , População BrancaRESUMO
BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACE-I(s)) and angiotensin receptor blockers (ARB(s)) provide vascular protection. This study was designed to compare ACE-I(s) with widely differing tissue affinity (captopril and quinapril) and an ARB (losartan) on vascular protection against the adverse effects of high cholesterol. METHODS AND RESULTS: Forty-two New Zealand rabbits on a 0.5% cholesterol diet were randomized into control, captopril (10 mg/kg/d), quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril, quinapril, and losartan significantly attenuated aortic lipid lesions (P=0.001). Captopril and quinapril were more effective than losartan in preserving vascular relaxation. CONCLUSIONS: Captopril, quinapril, and losartan had similar protective effects against atherogenesis. Captopril and quinapril were more effective than losartan in preserving vascular function. Increased bradykinin by ACE inhibition may be responsible for this improved vascular endothelial function.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Arteriosclerose/prevenção & controle , Tetra-Hidroisoquinolinas , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Arteriosclerose/fisiopatologia , Captopril/farmacologia , Captopril/uso terapêutico , Colesterol/sangue , Modelos Animais de Doenças , Isoquinolinas/farmacologia , Isoquinolinas/uso terapêutico , Cininas/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Óxido Nítrico/metabolismo , Quinapril , Coelhos , Receptores de Angiotensina/metabolismoRESUMO
BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.
Assuntos
Arteriosclerose/etiologia , Nicotina/farmacologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Arteriosclerose/sangue , Arteriosclerose/patologia , Cotinina/sangue , Dieta Aterogênica , Progressão da Doença , Técnicas In Vitro , Lipídeos/sangue , Masculino , Nicotina/sangue , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Coelhos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacosAssuntos
Cardiologia/normas , Ética Médica , Fraude/legislação & jurisprudência , Prática de Grupo/normas , Encaminhamento e Consulta/legislação & jurisprudência , Cirurgia Torácica , Cardiologia/economia , Conflito de Interesses , Prática de Grupo/economia , Humanos , Encaminhamento e Consulta/economia , Cirurgia Torácica/economia , Estados UnidosAssuntos
Cardiologia/normas , Competência Clínica , Médicos/psicologia , Papel (figurativo) , HumanosAssuntos
Conflito de Interesses , Guias como Assunto/normas , Pesquisa/normas , Má Conduta Científica , Revelação da Verdade , Academias e Institutos/organização & administração , Humanos , National Institutes of Health (U.S.)/organização & administração , Inovação Organizacional , Política Organizacional , Apoio à Pesquisa como Assunto/organização & administração , Faculdades de Medicina/organização & administração , Estados UnidosAssuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Digoxina/uso terapêutico , Modelos Animais de Doenças , Diuréticos/uso terapêutico , Endotelinas/antagonistas & inibidores , Etanercepte , Insuficiência Cardíaca/metabolismo , Humanos , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Camundongos , Camundongos Transgênicos , Neprilisina/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores do Fator de Necrose Tumoral/uso terapêutico , Espironolactona/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A previous study by our group showed that 10 weeks of pretreatment with losartan reduced myocardial infarct size and arrhythmias in a rat model of ischaemia-reperfusion. However, the effect of a differing time course of pretreatment has not been investigated. 104 Sprague-Dawley rats were randomised to four groups: a control, and three treatment groups in which losartan (40 mg/kg/day) was administered in drinking water for one day, one week, and four weeks respectively. After different durations of pretreatment, the rats were subjected to 17 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Haemodynamic variables were not significantly different between the four groups. Myocardial infarct size was unchanged after one day and one week of pretreatment (52+/-7, 57+/-6% vs.control 55+/-3%), but was significantly reduced by four weeks of pretreatment with losartan (38+/-6, p<0.05). Endothelial-dependent vasorelaxation was significantly increased by four weeks of pretreatment (-81+/-4 vs.-62+7%, p<0.05). As an indicator of ischaemia, vascular endothelial growth factor (VEGF) levels in ischaemic myocardium were decreased after one and four weeks of pretreatment (0.75+/-0.05, 0.58+/-0.10 vs. 1.0, p<0.05,0.01, respectively). In conclusion, losartan has time-dependent cardiovascular protective effects. Four weeks of pretreatment with losartan decreased infarct size and VEGF, and improved endothelial dysfunction.