Role of hyperglycaemia in the pathogenesis of hypotension observed in type-1 diabetic rats

The role of hyperglycaemia in the pathogenesis of hypotension in diabetic disorders was investigated using the changes in cardiac M₂-muscarinic receptor (M₂-mAChR) gene expression in type-1-like diabetic rats and cultured cardiomyocytes. Blood pressure was markedly decreased in diabetic rats following the intravenous injection of streptozotocin (STZ) for 8 weeks. Also, the baroreflex sensitivity (ΔHR/ΔBP), as measured by the changes in heart rate (ΔHR) and mean blood pressure (ΔBP) 1 min after the intravenous injection of phenylephrine (10 μg/kg), was significantly increased. Arecaidine propargyl ester (APE), a M₂-mAChR agonist produced a marked reduction in heart rate in these diabetic rats. Normalization of plasma glucose in diabetic rats using insulin (0.5 IU) or phlorizin (1 mg/kg) injection attenuated the blood pressure reduction and reversed the mRNA and protein levels of cardiac M₂-mAChR. A high concentration of glucose (20 mmol/l) directly influenced the increase in gene expression of M ₂-mAChR in the H9c2 cardiac cell line. Hyperglycaemia induced an increase in cardiac M₂-mAChR gene expression, suggesting a role in the pathogenesis of hypotension in diabetic disorders.