RESUMEN
To analyze the long-term effects of early overfeeding on the heart and coronary circulation, the effect of ischemia-reperfusion (I/R) and the role of the renin-angiotensin system (RAS) was studied in isolated hearts from control and overfed rats during lactation. On the day of birth litters were adjusted to twelve pups per mother (controls) or to three pups per mother (overfed). At 5 months of age, the rats from reduced litters showed higher body weight and body fat than the controls. The hearts from these rats were perfused in a Langendorff system and subjected to 30 min of ischemia followed by 15 min of reperfusion (I/R). The myocardial contractility (dP/dt) and the coronary vasoconstriction to angiotensin II were lower, and the expression of the apoptotic marker was higher, in the hearts from overfed rats compared to controls. I/R reduced the myocardial contractily, the coronary vasoconstriction to angiotensin II and the vasodilatation to bradykinin, and increased the expression of (pro)renin receptor and of apoptotic and antiapoptotic markers, in both experimental groups. I/R also increased the expression of angiotensinogen in control but not in overfed rats. In summary, the results of this study suggest that early overnutrition induces reduced activity of the RAS and impairment of myocardial and coronary function in adult life, due to increased apoptosis. Ischemia-reperfusion produced myocardial and coronary impairment and apoptosis, which may be related to activation of RAS in control but not in overfed rats, and there may be protective mechanisms in both experimental groups.
Asunto(s)
Envejecimiento/patología , Corazón/fisiopatología , Hipernutrición/metabolismo , Sistema Renina-Angiotensina , Envejecimiento/metabolismo , Angiotensina II/sangre , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Biomarcadores/metabolismo , Bradiquinina/farmacología , Conducta Alimentaria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Técnicas In Vitro , Inflamación/patología , Leptina/sangre , Masculino , Miocardio/metabolismo , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , Hipernutrición/sangre , Hipernutrición/fisiopatología , Perfusión , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Factores de Tiempo , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Obesity during childhood has dramatically increased worldwide in the last decades. Environmental factors acting early in life, including nutrition, play an important role in the pathogenesis of obesity and cardiovascular diseases in adulthood. AIMS: To analyze the effects of early overfeeding on the heart and coronary circulation, the effect of ischemia-reperfusion (I/R) and the role of the renin-angiotensin system (RAS) were studied in isolated hearts from control and overfed rats during lactation. METHODS AND RESULTS: On the day of birth litters were adjusted to twelve pups per mother (control) or to three pups per mother (overfed). At weaning (21 days) the rats were killed and the heart perfused in a Langendorff system and subjected to 30 min of ischemia followed by 15 min of reperfusion. The contractility (left developed intraventricular pressure) was lower in the hearts from overfed rats, and was reduced by I/R in hearts from control but not from overfed rats. I/R also reduced the coronary vasoconstriction to angiotensin II more in hearts from control than from overfed rats, and the vasodilatation to bradykinin similarly in both experimental groups. The expression of both angiotensin AGTRa and AGTR2 receptors was increased in the myocardium of overfed rats, and I/R increased the expression of both receptors in control rats but reduced it in overfed rats. The expression of apoptotic and antiapoptotic markers was increased in hearts of overfed rats compared with control, and further increased by I/R. CONCLUSIONS: These results suggest that both overfeeding and I/R impair cardiac and coronary function due, at least in part, to activation of the angiotensin pathway. However, overfeeding may reduce the impairment of ventricular contractility by I/R.
Asunto(s)
Contracción Miocárdica/fisiología , Reperfusión Miocárdica/efectos adversos , Hipernutrición/metabolismo , Receptores de Angiotensina/metabolismo , Vasodilatación/fisiología , Análisis de Varianza , Animales , Animales Lactantes , Immunoblotting , Tamaño de la Camada , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Diadenosine triphosphate (Ap3A) is a vasoactive mediator stored in platelet granules that may be released during coronary ischemia-reperfusion. To study its coronary effects in such circumstances, rat hearts were perfused in a Langendorff preparation and the coronary response to Ap3A (10(-7)-10(-5) mol/L) was recorded. Both at basal coronary resting tone and after precontraction with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F(2)(α) (U46619), Ap3A produced concentration-dependent vasodilation in the heart, which was attenuated following ischemia-reperfusion. Ap3A-induced relaxation was also attenuated in control conditions and after ischemia-reperfusion by the purinergic P2Y antagonist reactive blue 2 (2 × 10(-6) mol/L), the P2Y(1) antagonist MRS 2179 (10(-5) mol/L), the nitric oxide synthesis inhibitor N-omega-nitro-l-arginine methyl ester (l-NAME; 10(-4) mol/L) and the ATP-dependent potassium channel blocker glibenclamide (10(-5) mol/L). These results suggest that Ap3A induces coronary vasodilation, an effect attenuated by ischemia-reperfusion due to the functional impairment of purinergic P2Y receptors and K(ATP) channels, and/or reduced nitric oxide release. This impairment of vasodilation may contribute to the coronary dysregulation that occurs during ischemia-reperfusion.