Effect of long-term diabetes on serotonin-mediated contraction in carotid arteries from streptozotocin-induced diabetic male and female rats

An accumulating body of evidence suggests that males and females differ in vascular function in arteries under pathophysiological states. In this study, we tested whether there was a sex difference associated with serotonin (5-hydroxytryptamine, 5-HT)-mediated contraction in the carotid arteries of long-term streptozotocin (STZ)-induced diabetic rats [viz. 23 or 24 weeks after STZ (65 mg/kg, intravenously (i.v.)) injection starting at 8 weeks old of rats]. In the control group, the 5-HT- and high-K⁺-induced contractions were greater in females than in males. In both sexes, treatment with STZ led to a decrease of 5-HT-induced contraction in carotid arteries compared to controls. In STZ-induced diabetic rats, the carotid arterial 5-HT-induced contraction was greater in female rats than in diabetic male rats. The high-K⁺-induced contraction was greater in diabetic female rats than in either age-matched female controls or diabetic male rats. Expression of the 5-HT_2A receptor, which is the main receptor for 5-HT-induced contraction in rat carotid arteries, was similar among the four groups. These results suggest that decreased 5-HT-induced carotid arterial contraction is seen in both sexes under long-term STZ-induced diabetic conditions. Further, this reduction seems to be weaker in females than in males. This alteration of 5-HT-induced contraction may be partly associated with increased voltage-dependent Ca²⁺ channel activity.