RESUMO
Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.
Assuntos
Cardiomegalia/dietoterapia , Cardiotônicos/uso terapêutico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/uso terapêutico , Coração/fisiopatologia , Miocárdio/metabolismo , Animais , Aorta Abdominal/cirurgia , Débito Cardíaco , Cardiomegalia/fisiopatologia , Cardiotônicos/efeitos adversos , Cardiotônicos/química , Cardiotônicos/metabolismo , Constrição , Circulação Coronária , Metabolismo Energético , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/efeitos adversos , Óleos de Peixe/química , Óleos de Peixe/metabolismo , Insuficiência Cardíaca/prevenção & controle , Masculino , Contração Miocárdica , Consumo de Oxigênio , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
We have reported that dietary fish oil (FO) leads to the incorporation of long-chain n-3 PUFA into the gut tissue of small animal models, affecting contractility, particularly of rat ileum. This study examined the FO dose response for the incorporation of n-3 PUFA into ileal tissue and how this correlated with in vitro contractility. Groups of ten to twelve 13-wk-old Wistar-Kyoto rats were fed 0, 1, 2.5, and 5% FO-supplemented diets balanced with sunflower seed oil for 4 wk, after which ileal total phospholipid FA were determined and in vitro contractility assessed. For the total phospholipid fraction, increasing the dietary FO levels led to a significant increase first evident at 1% FO, with a stepwise, nonsaturating six-fold increase in n-3 PUFA as EPA (20:5n-3), DPA (docosapentaenoic acid, 22:5n-3), and DHA, but mainly as DHA (22:6n-3), replacing the n-6 PUFA linoleic acid (18:2n-6) and arachidonic acid (20:4n-6) over the dosage range. There was no difference in KCl-induced depolarization-driven contractility. However, a significant increase in receptor-dependent maximal contractility occurred at 1% FO for carbachol and at 2.5% FO for prostaglandin E2, with a concomitant increase in sensitivity for prostaglandin E2 at 2.5 and 5% FO. These results demonstrate that significant increases in ileal membrane n-3 PUFA occurred at relatively low doses of dietary FO, with differential receptor-dependent increases in contractility observed for muscarinic and prostanoid agonists.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Óleos de Peixe/farmacologia , Íleo/efeitos dos fármacos , Fosfolipídeos/metabolismo , Animais , Carbacol/farmacologia , Dinoprostona/farmacologia , Ácidos Docosa-Hexaenoicos , Relação Dose-Resposta a Droga , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/metabolismo , Íleo/metabolismo , Técnicas In Vitro , Masculino , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Contração Muscular/efeitos dos fármacos , Fosfolipídeos/química , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos WKY , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
We have reported that dietary fish oil (FO) rich in n-3 PUFA modulates gut contractility. It was further demonstrated that the gut of spontaneously hypertensive rats (SHR) has a depressed contractility response to prostaglandins (PG) compared with normotensive Wistar-Kyoto (WKY) rats. We investigated whether feeding diets supplemented with n-3 PUFA increased gut contractility and restored the depressed prostanoid response in SHR gut. Thirteen-week-old SHR were fed diets containing fat at 5 g/100 g as coconut oil (CO), lard, canola oil containing 10% (w/w) n-3 FA as alpha-linolenic acid (1 8:3n-3), or FO (as HiDHA, 22:6n-3) for 12 wk. A control WKY group was fed 5 g/100 g CO in the diet. As confirmed, the SHR CO group had a significantly lower gut response to PGE2 and PGF2alpha compared with the WKY CO group. Feeding FO increased the maximal contraction response to acetylcholine in the ileum compared with all diets and in the colon compared with lard, and restored the depressed response to PGE2 and PGF2alpha in the ileum but not the colon of SHR. FO feeding also led to a significant increase in gut total phospholipid n-3 PUFA as DHA (22:6n-3) with lower n-6 PUFA as arachidonic acid (20:4n-6). Canola feeding led to a small increase in ileal EPA (20:5n-3) and DHA and in colonic DHA without affecting contractility. However, there was no change in ileal membrane muscarinic binding properties due to FO feeding. This report confirms that dietary FO increases muscarinic- and eicosanoid receptor-induced contractility in ileum and that the depressed prostanoid response in SHR ileum, but not colon, is restored by tissue incorporation of DHA as the active nutrient.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Óleos de Peixe/farmacologia , Íleo/fisiologia , Contração Muscular/efeitos dos fármacos , Prostaglandinas/farmacologia , Animais , Colo/efeitos dos fármacos , Colo/fisiologia , Gorduras Insaturadas na Dieta/administração & dosagem , Dinoprosta/farmacologia , Dinoprostona/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/administração & dosagem , Íleo/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia , RatosRESUMO
Dietary saturated fat (SF) has adverse effects on cardiac and vascular smooth muscle (VSM) contractility. Furthermore, VSM of spontaneously hypertensive rats (SHR) is overreactive to various biological stimuli. The aim of this study was to investigate the effects of increasing dietary fat as lard on gut contractility in SHR. Control Wistar-Kyoto (WKY) rats and SHR (13 wk old) were fed for 12 wk a diet containing 3% sunflower oil [low fat (LF), 3% total fat] or diets supplemented with 7% lard [medium fat (MF), 10% total fat] or 27% lard [high fat (HF), 30% total fat]. For ileal and colonic tissues (WKY and SHR), there was a lower total phospholipid PUFA (n-6)/(n-3) ratio with increased dietary SF (P < 0.003). For WKY, increasing SF led to lower levels of the major SCFA and lower total SCFA levels in cecal digesta (P < 0.01). This trend was evident in SHR but significant only for butyrate (P < 0.01). Contractility responses were unaltered in ileum. In colon, there was a change of sensitivity (50% effective concentration) to angiotensin II in WKY (P < 0.05) due to increased SF and a change of sensitivity to prostaglandin (PG)E(2) and carbachol in SHR (P < 0.05). When the 3 dietary groups were combined, there was lower sensitivity (P < 0.01) and lower maximal contraction (P < 0.05) in ileum and lower maximal contraction in colon of SHR in response to PGF(2alpha) (P < 0.05) and PGE(2) (P < 0.01) compared with WKY. Unlike (n-3) PUFA, dietary SF had little overall effect on gut contractility. However, this is the first report of a defect in PG responsiveness from gut tissue from hypertensive rats.