Effects of Diabetes Mellitus, Pressure-Overload and Their Association on Myocardial Structure and Function

Abstract

Background

Structural and functional changes involved in cardiac injury induced by diabetes mellitus, pressure-overload, or both conditions were evaluated.

Methods

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).

Results

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 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.

Conclusion

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.

American Journal of Hypertension 2009; 22:1190–1198 © 2009 American Journal of Hypertension, Ltd.

© American Journal of Hypertension, Ltd. 2009