ABSTRACT
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.
Subject(s)
Endothelium, Vascular/drug effects , Pulmonary Artery/drug effects , Tobacco Smoke Pollution/adverse effects , Vasodilation/drug effects , Animals , Arginase/metabolism , Arginine/pharmacology , Female , Nitric Oxide Synthase/metabolism , Nitroglycerin/pharmacology , RatsSubject(s)
Black People , Cardiovascular Diseases/genetics , Cardiovascular Diseases/prevention & control , Health Education/organization & administration , Health Promotion/organization & administration , Black or African American/statistics & numerical data , Age Distribution , Aged , Cardiology , Cardiovascular Diseases/epidemiology , Drug Industry , Female , Humans , Male , Middle Aged , Prevalence , Research Support as Topic , Risk Factors , Sex Distribution , Societies, Medical , United States/epidemiology , White PeopleSubject(s)
Cardiology Service, Hospital , Medical Staff, Hospital , Humans , Internship and Residency , WorkforceABSTRACT
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.
Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Arteriosclerosis/prevention & control , Tetrahydroisoquinolines , Vasoconstriction/drug effects , Vasodilation/drug effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Arteriosclerosis/physiopathology , Captopril/pharmacology , Captopril/therapeutic use , Cholesterol/blood , Disease Models, Animal , Isoquinolines/pharmacology , Isoquinolines/therapeutic use , Kinins/metabolism , Losartan/pharmacology , Losartan/therapeutic use , Male , Nitric Oxide/metabolism , Quinapril , Rabbits , Receptors, Angiotensin/metabolismABSTRACT
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.
Subject(s)
Arteriosclerosis/etiology , Nicotine/pharmacology , Tobacco Smoke Pollution/adverse effects , Animals , Aorta/drug effects , Aorta/pathology , Arteriosclerosis/blood , Arteriosclerosis/pathology , Cotinine/blood , Diet, Atherogenic , Disease Progression , In Vitro Techniques , Lipids/blood , Male , Nicotine/blood , Pulmonary Artery/drug effects , Pulmonary Artery/pathology , Rabbits , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacology , Vasomotor System/drug effectsSubject(s)
Cardiology/standards , Ethics, Medical , Fraud/legislation & jurisprudence , Group Practice/standards , Referral and Consultation/legislation & jurisprudence , Thoracic Surgery , Cardiology/economics , Conflict of Interest , Group Practice/economics , Humans , Referral and Consultation/economics , Thoracic Surgery/economics , United StatesSubject(s)
Coronary Circulation , Tobacco Smoke Pollution/adverse effects , Blood Pressure , Heart Rate , HumansSubject(s)
Conflict of Interest , Guidelines as Topic/standards , Research/standards , Scientific Misconduct , Truth Disclosure , Academies and Institutes/organization & administration , Humans , National Institutes of Health (U.S.)/organization & administration , Organizational Innovation , Organizational Policy , Research Support as Topic/organization & administration , Schools, Medical/organization & administration , United StatesSubject(s)
Heart Failure/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Digoxin/therapeutic use , Disease Models, Animal , Diuretics/therapeutic use , Endothelins/antagonists & inhibitors , Etanercept , Heart Failure/metabolism , Humans , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/therapeutic use , Mice , Mice, Transgenic , Neprilysin/antagonists & inhibitors , Randomized Controlled Trials as Topic , Receptors, Tumor Necrosis Factor/therapeutic use , Spironolactone/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolismSubject(s)
Family Relations , Parenting/psychology , Physician's Role , Cardiology , Humans , United States , Workload/psychologySubject(s)
Cardiology , Manuscripts, Medical as Topic , Periodicals as Topic , Publishing , Humans , United StatesABSTRACT
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.