Effects of brain natriuretic peptide on contraction and intracellular Ca²⁺ in ventricular myocytes from the streptozotocin-induced diabetic rat

The streptozotocin (STZ)-treated rat is a widely studied experimental model of diabetes mellitus (DM). Its pathophysiology includes hypoinsulinemia, hyperglycemia, cardiac hypertrophy, and a cardiomyopathy that is characterized by the presence of diastolic and/or systolic contractile dysfunction. As part of their endocrine function cardiomyocytes in the heart produce and secrete a family of related peptide hormones called the natriuretic peptides that include A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). ANP and BNP levels are variously augmented in patients with hypertension, cardiac overload, in the ventricles of failing or hypertrophied heart, in cardiac heart failure, in acute myocardial infarction (MI), and in some circumstances in DM. In this article, the effects of BNP on ventricular myocyte contraction and Ca²⁺ transport in STZ-induced diabetic rats have been investigated. BNP concentration was significantly increased in blood plasma and in atrial muscle in STZ-induced diabetic rats compared to age-matched controls. BNP was 11.9 ± 0.9 ng/mL in plasma from diabetic rats compared to 6.7 ± 1.6 ng/mL in controls and 15.8 ± 2.0 ng/mg protein in diabetic atrial muscle compared to 8.5 ± 1.0 ng/mg protein in controls. The heart weight to body weight ratio, an indicator of hypertrophy, was significantly increased in diabetic rat heart (4.3 ± 0.1 mg/g) compared to controls (3.7 ± 0.04 mg/g). The amplitude of shortening was not significantly altered in diabetic myocytes (10.3 ± 0.4%) compared to controls (10.9 ± 0.4%). BNP reduced the amplitude of shortening to a greater extent in diabeticmyocytes (8.1 ± 0.6%) compared to controls (10.1 ± 0.4%). The time to peak (TPK) shortening was significantly prolonged in diabetic myocytes (254 ± 8 ms) compared to controls (212 ± 5 ms) and was not additionally altered by BNP. The time to half relaxation of shortening was also significantly prolonged in diabetic myocytes (131 ± 8 ms) compared to controls (111 ± 5 ms). BNP (10^-8 to 10^-6 M) normalized the time to half relaxation of shortening in diabetic myocytes to that of controls. Time to peak (TPK) shortening of Ca²⁺ was not different between diabetic and control rats. However, BNP (10^-7 M) increases TPK of Ca²⁺ significantly. The amplitude of the Ca ²⁺ transient was significantly increased in diabetic myocytes (0.42 ± 0.02 Ratio units [RU]) compared to controls (0.36 ± 0.02 RU) and was not additionally altered by BNP. BNP may have a protective role in STZ-induced diabetic rat heart.