Effects of diabetes mellitus, pressure-overload and their association on myocardial structure and function

Abstract

BackgroundStructural and functional changes involved in cardiac injury induced by diabetes mellitus, pressure-overload, or both conditions were evaluated.MethodsPressure-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).ResultsCompared 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 endproduct (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.ConclusionLong-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. © 2009 American Journal of Hypertension, Ltd.