The effect of long-term streptozotocin-induced diabetes on contractile andrelaxation 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 co ntractile responses of isolated coronary arteries to seven different vasoac tive agents. 2 The average fasting and non-fasting blood glucose concentrations (mM) wer e 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 (H bA(1)) was also significantly (P < 0.0001) increased in STZ-induced diabeti c 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 betwe en the HbA(1) levels and maximal responses or sensitivities to the vasoacti ve agents. 3 The maximal relaxation induced by rat-alpha calcitonin gene-related pepti de (rat-alpha CGRP) was significantly attenuated in the coronary arteries o f 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 signific ant difference in the sensitivity to rat-alpha CGRP between the two groups. 4 There was no significant difference in either maximal response or sensiti vity to any of the six other vasoactive agents between STZ- induced diabeti c 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-induc ed relaxation in the intramural coronary arteries or Wistar rats.