This study aimed to investigate whether the 5-HT2 receptor blockade alters the
5-HT effect on vascular sympathetic neurotransmission and platelet activation in
type 1 diabetes. 28-day diabetes was obtained by
alloxan (150 mg/kg; s.c.) in male Wistar rats, administering
sarpogrelate (5-HT2 blocker; 30 mg/kg/day; p.o.) for 14 days.
Blood glucose and
body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet
5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and
sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous
noradrenaline administration, examining the induced
vasoconstrictor responses.
Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain,
hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma
5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in
sarpogrelate-treated diabetic rats.
5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT1D or 5-HT7 antagonists (
LY310762 or
SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719.
Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day
sarpogrelate treatment improves
polydipsia and
polyuria, reduces platelet hyperactivation, plasma
5-HT and the vascular sympathetic tone, and changes
5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT1D/7 are involved in the sympatho-inhibition.