Alterations in Atrial Natriuretic Peptide and Its Receptor Levels in Long‐Term, Streptozotocin‐Induced, Diabetes in Rats

Abstract

Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro- and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long-term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)-induced 8-month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ-induced, 8-month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ-induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma (P < 0.05), kidney (P < 0.01), heart atria (P < 0.05), and ventricles (P < 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex (P < 0.05), juxtaglomerular medulla (P < 0.05), and papilla (P < 0.05) of 8-month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ-induced diabetic heart merits additional study.

Endoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic rats

“…These findings indicate that a hyperglycemia environment induce ER-dependent death pathway activity, leading to apoptosis. To our knowledge, in normal heart, synthesis of secretory proteins is not a major function of a cardiac myocyte, but with the development of cardiomyopathy in diabetes, the heart could become a neuroendocrine organ attributed to prolonged elevation of protein synthesis such as atrial natriuretic peptide and brain natriuretic peptide (Howarth et al 2006, Obineche et al 2006 and together with other strong inducers we suggested in the introduction that the ERS may participate in the beginning of diabetic cardiomyopathy. Compared with other mechanisms, involved in the diabetic myocardial cell, ERS may have crosstalk with them; this means that ERS is not only parallel with them but also as a result and mediator for other ways to apoptosis.…”

Murine Models of Heart Failure With Preserved Ejection Fraction

“…Streptozotocin-injected rats exhibit many of the cardiovascular complications found in humans with both type 1 and type 2 diabetes. They have increased levels of cardiac and circulating natriuretic peptides 192 , 193 and inflammatory markers, such as interleukin 1, interleukin 6, and intracellular adhesion molecule 1 (194) . Blood pressure remains within normal ranges, indicating that hyperglycemia alone may be sufficient to account for the observed changes seen in the heart in this model (17) .…”

Activation of soluble guanylyl cyclase signalling with cinaciguat improves impaired kidney function in diabetic mice

“…Therefore, treatment with cinaciguat showed also only a slight, non‐significant induction of cGMP excretion in diabetic eNOS KO animals. Natriuretic peptides are enhanced under diabetic conditions (Malek et al, 2019; Moore et al, 2007; Obineche et al, 2006) and are mainly responsible for release of extracellular cGMP (Chaykovska et al, 2018). So, urinary cGMP probably come mainly from particulate GC signalling and high cGMP concentrations in urine of eNOS KO mice arise from a counterregulation due to reduced NO/sGC signalling.…”