Falcão-Pires Inês, Gonçalves Nádia, Moura Cláudia, Lamego Inês, Eloy Catarina, Lopes José M, Begieneman Mark P V, Niessen Hans W M, Areias José C, Leite-Moreira Adelino F
Department of Physiology, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal.
Am J Hypertens. 2009 Nov;22(11):1190-8. doi: 10.1038/ajh.2009.159. Epub 2009 Sep 10.
Structural and functional changes involved in cardiac injury induced by diabetes mellitus, pressure-overload, or both conditions were evaluated.
Pressure-overload was established by suprarenal aortic banding in rats. Six weeks later, diabetes was induced by streptozotocin (STZ, 65 mg/kg, intraperitoneally), resulting in four groups: SHAM, banded (BA), diabetic (DM), and diabetic-banded (DM-BA). On the 12th week, left ventricular (LV) structure and function were evaluated. LV function was assessed in vivo with pressure-volume catheters and in vitro by papillary muscles' performance at baseline and in response to isoprenaline (ISO, 10(-8) to 10(-5) M).
Compared to SHAM, we observed a significant increase of type-B natriuretic peptide (BA = 370 +/- 110%; DM-BA = 580 +/- 210%), LV mass (BA = 36.8 +/- 3.6%; DM-BA = 32.1 +/- 3.1%), cardiomyocyte diameter (BA = 19.5 +/- 2.3%; DM = 14.3 +/- 1.9%; DM-BA = 11.4 +/- 2.0%), fibrosis (BA = 85 +/- 14%; DM = 145 +/- 28%; DM-BA = 155 +/- 14%), advanced glycation end-product (AGE) deposition (DM = 141 +/- 29%; DM-BA = 166 +/- 46%), contraction (tAT: DM = 13.7 +/- 2.4%; DM-BA = 26.3 +/- 7.1%); a delayed relaxation (tHR: DM = 13.8 +/- 2.6%; DM-BA = 25.5 +/- 9.2%) and a decrease of collagen type-I/type-III ratio (DM = -66.1 +/- 4.6%; DM-BA = -51.9 +/- 5.5). In SHAM animals, ISO (10(-5) M) increased 86.5 +/- 26.2% active tension, 105.3 +/- 20.2% dT/dt(max), and 166.8 +/- 29.9% dT/dt(min). Similar effects were observed in BA and DM animals, whereas in DM-BA these inotropic and lusitropic responses were blunted. Moreover, at a similar resting muscle length, ISO decreased passive tension by 12 +/- 3% in SHAM and 11 +/- 3% in BA, indicating an increase in myocardial distensibility, an effect that was absent in both diabetic groups.
Long-standing pressure-overload increased LV mass, while diabetes promoted AGE and collagen deposition, which might explain the abolition of ISO-induced increased myocardial distensibility. Association of pressure-overload and diabetes completely blunted the inotropic and lusitropic responses to ISO, with no additional structural damages than in pressure-overload or diabetes alone.
评估了糖尿病、压力超负荷或两者共同导致的心脏损伤所涉及的结构和功能变化。
通过对大鼠进行肾上腺主动脉缩窄建立压力超负荷模型。六周后，腹腔注射链脲佐菌素（STZ，65mg/kg）诱导糖尿病，从而形成四组：假手术组（SHAM）、缩窄组（BA）、糖尿病组（DM）和糖尿病缩窄组（DM-BA）。在第12周时，评估左心室（LV）的结构和功能。使用压力-容积导管在体内评估左心室功能，并通过乳头肌在基线状态及对异丙肾上腺素（ISO，10(-8)至10(-5)M）反应时的表现进行体外评估。
与假手术组相比，我们观察到B型利钠肽显著增加（BA = 370±110%；DM-BA = 580±210%）、左心室质量增加（BA = 36.8±3.6%；DM-BA = 32.1±3.1%）、心肌细胞直径增加（BA = 19.5±2.3%；DM = 14.3±1.9%；DM-BA = 11.4±2.0%）、纤维化增加（BA = 85±14%；DM = 145±28%；DM-BA = 155±14%）、晚期糖基化终末产物（AGE）沉积增加（DM = 141±29%；DM-BA = 166±46%）、收缩（tAT：DM = 13.7±2.4%；DM-BA = 26.3±7.1%）；舒张延迟（tHR：DM = 13.8±2.6%；DM-BA = 25.5±9.2%）以及I型/III型胶原比例降低（DM = -66.1±4.6%；DM-BA = -51.9±5.5）。在假手术组动物中，ISO（10(-5)M）使主动张力增加86.5±26.2%、dT/dt(max)增加105.3±20.2%、dT/dt(min)增加166.8±29.9%。在缩窄组和糖尿病组动物中观察到类似效应，而在糖尿病缩窄组中这些变力性和变时性反应减弱。此外，在相似的静息肌肉长度下，ISO使假手术组的被动张力降低12±3%，缩窄组降低11±3%，表明心肌伸展性增加，而这一效应在两个糖尿病组中均未出现。
长期压力超负荷增加了左心室质量，而糖尿病促进了AGE和胶原沉积，这可能解释了ISO诱导的心肌伸展性增加消失的原因。压力超负荷与糖尿病共同作用使对ISO的变力性和变时性反应完全减弱，与单独的压力超负荷或糖尿病相比，没有额外的结构损伤。
