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Abstract
The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT3) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT2A antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT1B and 2B antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT7 and antagonists at the 5-HT2B may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.