RESUMEN
We investigated the relationship between left ventricular diastolic function and interstitial collagen content in the endocardium, mesocardium and epicardium of transverse sections of the heart, using an image analysis system in normotensive and hypertensive long-term streptozotocin (STZ) diabetic rats. STZ-induced diabetes was characterised by elevated blood glucose, polyuria, polydypsia and loss of body weight. In vivo systolic blood pressure was 165 +/- 4, 136 +/- 3 and 129 +/- 7 mmHg in hypertensive and normotensive diabetic rats and age-matched controls, respectively. Heart rate was significantly lower (P < 0.01) in diabetic rats (283 +/- 8 and 280 +/- 10 beats min-1 in normotensive and hypertensive rats, respectively) than controls (393 +/- 18 beats min-1). Pressure-volume (P-V) curves were studied in isolated Langendorff perfused hearts at rest and after 20 min global ischaemia and 30 min reperfusion 6 months after induction of diabetes. Left ventricular volumes were significantly smaller in diabetic rats than age-matched controls, but volumes normalised for heart weight were higher in normotensive (by 28%) and hypertensive (by 10%) diabetic rats. Slopes of end-diastolic P-V curves were similar between groups in basal conditions, but left ventricular systolic P-V curves were steeper in normotensive and flatter in hypertensive diabetic hearts. Post-ischaemic left ventricular end-diastolic pressure was significantly higher than the pre-ischaemic value at comparable increments of volume in each group. Collagen content significantly increased in the heart of rats with STZ-diabetes both in the free left ventricular wall and septum, and suggested this may play a role in the cardiac defects in contractility and relaxation in our experimental conditions. These results indicate that diabetes, irrespective of associated hypertension, can cause major changes in cardiac performance and susceptibility to ischaemia and reperfusion.
Asunto(s)
Colágeno/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/fisiopatología , Diástole/fisiología , Hipertensión/complicaciones , Hipertensión/fisiopatología , Animales , Velocidad del Flujo Sanguíneo/fisiología , Glucemia/metabolismo , Presión Sanguínea/fisiología , Peso Corporal/fisiología , Diabetes Mellitus Experimental/metabolismo , Endocardio/química , Endocardio/metabolismo , Hemoglobina Glucada/metabolismo , Corazón/anatomía & histología , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/química , Ventrículos Cardíacos/metabolismo , Hipertensión/metabolismo , Técnicas In Vitro , Masculino , Isquemia Miocárdica/fisiopatología , Tamaño de los Órganos/fisiología , Ratas , Daño por Reperfusión/fisiopatología , Volumen Sistólico/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/fisiología , Aumento de Peso/fisiologíaRESUMEN
We investigated the effects of angiotensin I (4 x 10(-9), 4 x 10(-8) and 4 x 10(-7) M) on myocardial contractility, heart rate and coronary perfusion in the isolated rat heart before and after inhibition of angiotensin-converting enzyme (ACE) by captopril (4 x 10(-4) M). We also studied the post-ischaemic recovery of cardiac function in isolated hearts subjected to global myocardial ischaemia and reperfused with various doses of angiotensin II (1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) M). Angiotensin I significantly reduced coronary flow, the vasoconstrictor effect of a second identical dose was attenuated after inhibition of ACE with captopril. Angiotensin II reduced coronary flow to the same extent as angiotensin I at a concentration four times lower. Left ventricular developed pressure was reduced by angiotensin I and angiotensin II in a dose-dependent manner. Heart rate was not affected by angiotensin I and was significantly lowered by the highest doses (1 x 10(-8) and 1 x 10(-7) M) of angiotensin II. Post-ischaemic recoveries of vascular and contractile function were similar in control hearts and in hearts given angiotensin II during reperfusion. However, left ventricular end-diastolic pressure was increased by the highest dose (1 x 10(-7) M) of angiotensin II throughout reperfusion compared with controls or hearts receiving lower doses (NS). In conclusion the attenuated vasoconstrictor response to angiotensin I after captopril pre-treatment confirms the existence of an intracardiac renin-angiotensin system operative in vitro. Our results also suggest that angiotensin II, at a high concentration, may play a negative role in relaxation in the ischaemic-reperfused injured heart.
Asunto(s)
Angiotensina II/farmacología , Angiotensina I/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/uso terapéutico , Corazón/efectos de los fármacos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Angiotensina I/uso terapéutico , Angiotensina II/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Perfusión , Ratas , Ratas Sprague-DawleyRESUMEN
We assessed the effects of idrapril, a novel angiotensin-converting enzyme inhibitor, and captopril in the isolated rat heart after ischaemia and reperfusion and measured angiotensin-converting enzyme activity in myocardial tissue. Hearts were perfused and subjected to global ischaemia and reperfusion. Idrapril (0.1, 1, 10, and 50 micrograms/ml), captopril (80 micrograms/ml) or vehicle were given before ischaemia and throughout reperfusion. Post-ischaemic recovery of coronary flow was significantly decreased with 50 micrograms/ml of idrapril (43 +/- 9% compared to 64 +/- 3% in controls) whereas heart rate was unaffected. Recovery of developed pressure and activity of cardiac angiotensin-converting enzyme were significantly reduced by idrapril in a dose-dependent manner. This study suggests that protection or lack of protection by idrapril on recovery of contractile function seems to depend on the degree of inhibition of tissue angiotensin-converting enzyme activity in the setting of acute heart ischaemic insult. Our results suggest that while a certain degree of inhibition of angiotensin-converting enzyme in the heart is beneficial, marked tissue inhibition may be deleterious.