Effect of sarpogrelate treatment on 5-HT modulation of vascular sympathetic innervation and platelet activity in diabetic rats

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway

“…This drug caused increased glycaemia after day 2 post-injection, with a consequent loss of weight. Hyperglycaemia stayed at the same rate during the 28-day period, whereas weight slightly increased, reaching values similar to those prior to alloxan administration [ 17 , 25 , 26 ].…”

“…exogenous NA are higher in diabetic than in normoglycaemic animals supports both the development of diabetic peripheral neuropathy and microvascular complications in the kidney [ 37 , 38 ]. Our group has already shown cardiovascular sympathetic overactivity as a marker of cardiovascular impairment in diabetes [ 22 , 25 , 26 ] or hypertension [ 39 ].…”

“…These data differ from the serotonergic sympatholytic effect at vascular level in a pharmacological-altered model, where both 5-HT 1 and 5-HT 7 receptor types were involved [ 24 ] in the inhibitory action. As currently, no selective 5-HT 5A receptor agonist is described, to study this receptor type effect, we utilised a 5-HT 5A selective serotonergic antagonist (SB 699551) prior to 5-CT administration [ 25 ]. As SB 699551 did not reverse 5-CT inhibitory action, we could devoid 5-HT 5A receptor type of any sympatholytic effect in the kidney vasculature of diabetic animals and confirm that the sole serotonergic receptor type involved in the sympatho-inhibitory effect on vasopressor responses is the 5-HT 1 receptor type, which is in agreement with previous results by our group at vascular level in normoglycaemic and diabetic rats [ 21 , 22 ], and at renal or mesenteric levels in normoglycaemic rats [ 18 , 19 ], but differs from those obtained in the mesentery of hypertensive rats, where 5-HT 4 was the responsible receptor type of the serotonergic inhibitory effect [ 39 ].…”

“…In this sense, 5-HT causes rat vascular sympatho-inhibition mainly by activation of 5-HT 1D receptors [ 18 , 19 , 21 ]. However, experimental diabetes, as well as pharmacological 5-HT modulation by the antagonism of 5-HT 2 receptor, modify the serotonergic effect on the sympathetic discharge of rat vasculature [ 22 , 23 , 24 , 25 ], maintaining the main vascular sympatholytic effect of 5-HT. Furthermore, the inhibition of 5-HT reuptake during diabetes crucially modifies serotonergic regulation of the noradrenergic system, showing both sympatholytic and sympatho-excitatory action [ 26 ].…”