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

1 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. 2 The average fasting and non-fasting blood glucose concentrations (mM) 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 (n = 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. 3 The maximal relaxation induced by rat-alpha calcitonin gene-related peptide (rat-alpha CGRP) 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-alpha CGRP between the two groups. 4 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). 5 Our results show that partially metabolic controlled long-term (34 weeks) STZ-induced diabetes causes a selective depression of rat-alpha CGRP-induced relaxation in the intramural coronary arteries or Wistar rats.