Cooling augments contractile response to 5-hydroxytryptamine via an endothelium-dependent mechanism.
The interaction between cooling and vasoactive substances, e.g. 5-hydroxytryptamine (5-HT), plays an important role in the pathophysiology of cold-induced vasospasm. Our objective was to study the effect of cooling on the 5-HT vascular response, classify the involved 5-HT receptors, and to analyze the role of the endothelium. Ring segments from the rat jugular vein, a preparation without alpha-adrenergic receptors, were suspended in organ baths to record the circular motor activity. The temperature was initially 37 degrees C and was thereafter either continuously lowered to 10 degrees C or kept constant at different temperatures within this range. 5-HT at low concentrations (10(-11) to 3 x 10(-8) M) induced relaxation at 37 degrees C in segments precontracted by prostaglandin F2 alpha. The relaxation was recognized to be mediated via an endothelium-dependent 5-HT1-like receptor mechanism presumably involving the release of endothelium-derived relaxing factor (EDRF). Cooling to 29 and 20 degrees C diminished the relaxation, probably due to an attenuated release of EDRF. 5-HT at concentrations of more than 10(-8) M induced a contraction in all vessels at 37 degrees C mediated via a 5-HT2 receptor. An increased 5-HT-induced contraction was seen at temperatures below 37 degrees C in vessels with an intact endothelium. Endothelial denudation diminished the cold-induced enhancement of the contraction to 5-HT. These studies suggest that endothelial mechanisms contribute to a cold-induced augmented response to 5-HT.
Bodelsson
M
M
Department of Surgery, Lund University, Sweden.
Arneklo-Nobin
B
B
Törnebrandt
K
K
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D013696:Temperature; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D012701:Serotonin