Cardiovascular Effects From Stimulation of 5‐hydroxytryptamine Receptors

Abstract

The cardiovascular effects of 5-hydroxytryptamine (5-HT), consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilatation or vasoconstriction, are mediated by three main types of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In intact animals 5-HT elicits a short-lasting bradycardia, accompanied by hypotension, via stimulation of 5-HT3 receptors located on sensory vagal nerve endings in the heart (Bezold-Jarisch reflex). The nature of 5-HT receptors mediating tachycardiac responses is species-dependent. Myocardial 5-HT1-like and 5-HT2 receptors subserve tachycardia in the cat and rat, respectively. Tachycardia in the dog and rabbit is due to a release of catecholamines effected via the 5-HT2 receptors on the adrenal medulla and the 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibres, respectively. The receptors mediating tachycardia in the pig are unique as they do not resemble any of the three 5-HT receptors characterized so far. The blood pressure response to 5-HT is usually triphasic: initial short-lasting hypotension due to reflex bradycardia (via 5-HT3 receptors), a middle pressor phase (via 5-HT2 receptors), and a longer-lasting hypotension (via 5-HT1-like receptors). Vascular contraction by 5-HT is generally mediated by 5-HT2 receptors (located primarily on the large conducting vessels), though in some instances (e.g., dog saphenous vein, dog and human basilar artery, and porcine arteriovenous anastomoses) the contractile response is (also) mediated via 5-HT1-like receptors. Venous dilatation and arteriolar dilatation (leading to increased capillary ['nutrient'] blood flow) occur via 5-HT1-like receptors located mainly on the vascular smooth muscles but also on the endothelium; the smooth muscle and endothelial 5-HT1-like receptors seem to be heterogeneous. In addition, 5-HT can elicit vasodilatation and hypotension as a result of decreased sympathetic nervous tone by acting within the central nervous system and by inhibiting noradrenaline release by a presynaptic action. Both these effects also involve 5-HT1-like receptors that do not appear to be identical. Last, knowledge of the cardiovascular effects of 5-HT and the nature of the receptors involved should be helpful in developing 5-HT-related compounds that may be useful in the treatment of hypertension, migraine, and peripheral vascular diseases.

Post exercise hypotension is not mediated by the serotonergic system in borderline hypertensive individuals

“…13 Both of these areas have minimal blood flow during exercise. Furthermore, peripheral 5-HT has been shown to act on 5-HT2 receptors and cause vasoconstriction 14,15 and is cleared rapidly via monoamine oxidase. 16 Therefore, the purpose of this investigation was to examine the effects of central 5-HT on the magnitude of the blood pressure decrements after acute exercise.…”

Sarpogrelate diminishes changes in energy stores and ultrastructure of the ischemic-reperfused rat heart

“…Serotonin is released upon platelet aggregation or resident cardiac mast cell degranulation (Rappaport et al 1948;Parikh and Singh 1997) and produces vasoconstrictor effects mediated partly by 5-HT 2A receptors (Saxena 1989;Nilsson et al 1999). Likewise, the cardiac stimulatory effects of serotonin (Fozard and Mwaluko 1976;Sakai and Akima 1979) in the heart are attributed to 5-HT 2 receptors present in cardiomyocytes (Hamamori et al 1990;Laer et al 1998).…”

5‐HT1‐like receptors mediate 5‐hydroxytryptamine‐induced contraction of guinea‐pig isolated iliac artery

“…Contractile responses of blood vessels to 5-hydroxytryptamine (5-HT) are mostly mediated by 5-HT2 receptors (for a review see Saxena, 1989). Notable exceptions are the dog isolated saphenous vein (Apperley et al, 1980;Feniuk et al, 1985;Humphrey et al, 1988), isolated basilar arteries from various species including man (Bradley et al, 1986b;Chang & Owman, 1989;Connor et al, 1989;, cranial arteriovenous anastomoses of pig and cat (Saxena et al, 1986;Feniuk et al, 1987) and dog carotid arterial bed .…”