GENDER DIFFERENCES INVOLVING SEROTONIN (5‐HT) RECEPTORS IN TYPE I DIABETIC RATS

Diabetes mellitus is an important topic of research. In both Type I and Type II diabetes vascular and renal dysfunction are some of the many negative impacts observed in diabetic patients. Increased plasma levels of 5‐HT exist in male diabetic rodent models and previous data in male Japanese diabetic patients demonstrated that inhibition of 5‐HT 2A receptors reduced proteinuria observed. Whether these are differences in males and females in 5‐HT levels and function is unknown. We hypothesized that increased levels 5‐HT receptors may be the cause of the vascular damage observed in diabetics; elevated levels of 5‐HT and 5‐HT receptors may lead to increased vasoconstriction. We used male and female Sprague‐Dawley rats (300–325g) and made them diabetic with Streptozotocin (STZ). At 14 days and 28 days post‐onset of diabetes we euthanized the animals, harvested tissues and blood vessels for Western blot and myograph analysis. At day 14, no significant differences in contractile responses in the blood vessels from either the male or female control vs diabetic rats in the thoracic aorta, renal, superior mesenteric, and femoral arteries existed. There was a leftward shift in the response curve to 5‐HT in the vessels from the males of both groups compared to the females. At day 28, there was an increased contractile response to 5‐HT in the aorta from the diabetic rats compared to control from male and females. The females also showed increased contraction to 5‐HT in the superior mesenteric artery at 28 days. There was no change observed in the renal artery or femoral artery from either sex at 28 days. We observed at days 14 and 28 in the aorta of the male rats that there was no differences in 5‐HT 2A or 5‐HT 2B receptor levels. In the kidney cortex at day 14 we observed increased expression of both 5‐HT 2A and 5‐HT 2B receptor levels. At day 28 only the 5‐HT 2B receptor in the kidney cortex from the diabetic rats was increased. There was no difference in the 5‐HT 2A receptor levels. In the aorta from the 14 day female rats we saw greater expression of the 5‐HT 2A receptor in the diabetic rats compared to control and less expression of the 5‐HT 2B receptor in the aorta from the diabetic rats compared to control. At 28 days we observed no difference between groups in the 5‐HT 2A receptor levels but a small increase in the levels of the 5‐HT 2B receptor in the aortas from the diabetic rats. In the cortex from the female rats we saw increased levels of the 5‐HT 2A receptor at both 14 and 28 days and increased levels of the 5‐HT 2B receptor levels at 28 days. These data clearly show altered expression of 5‐HT receptor during the development of diabetes and clear sex differences as well. Support or Funding Information Oakland University Center for Biomedical Research