The effect of long‐term streptozotocin‐induced diabetes on contractile and relaxation responses of coronary arteries: selective attenuation of CGRP‐induced relaxations

This study investigates the effect of partially metabolic controlled long‐term (34 weeks) streptozotocin (STZ)‐induced diabetes on relaxation and contractile responses of isolated coronary arteries to seven different vasoactive agents. The average fasting and non‐fasting blood glucose concentrations (m M ) were significantly elevated in STZ‐induced diabetic rats ( P <0.0001; 10.4±0.4 and 16.6±1.1, n =15) compared to those (4.3±0.03 and 4.7±0.18, n =11) in age‐matched controls. The level of glycated haemoglobin (HbA 1 ) was also significantly ( P <0.0001) increased in STZ‐induced diabetic rats. In STZ‐induced diabetic rats, the HbA 1 levels were significantly correlated with the non‐fasting blood glucose concentrations ( r =0.76; P =0.003; n =13). In both groups, there was no significant correlation between the HbA 1 levels and maximal responses or sensitivities to the vasoactive agents. The maximal relaxation induced by rat‐αcalcitonin gene‐related peptide (rat‐αCGRP) was significantly attenuated in the coronary arteries of STZ‐induced diabetic rats ( P <0.05; 40±7%, n =15) compared to that in age‐matched controls (63±3%, n =11). However, there was no significant difference in the sensitivity to rat‐αCGRP between the two groups. There was no significant difference in either maximal response or sensitivity to any of the six other vasoactive agents between STZ‐ induced diabetic rats ( n =15) and age‐matched controls ( n =11). Our results show that partially metabolic controlled long‐term (34 weeks) STZ‐induced diabetes causes a selective depression of rat‐αCGRP‐induced relaxation in the intramural coronary arteries of Wistar rats.British Journal of Pharmacology (2000) 129 , 1212–1218; doi: 10.1038/sj.bjp.0703159