Interactions between serotonin and endogenous and exogenous noradrenaline in the human forearm.
We investigated the interactions between serotonin (5-hydroxytryptamine, 5-HT) and exogenous or endogenous noradrenaline (NA) in the forearm of normotensive volunteers (n = 24), using venous occlusion plethysmography. Endogenous release of NA was stimulated by lower body negative pressure (LBNP; -10, -20 and -40 mmHg) and by intra-arterial (i.a.) infusions of tyramine (0.1 to 1 microgram/kg/min). Exogenous NA was infused in cumulative doses (0.3 to 10 ng/kg/min). All experiments were performed in the presence of either vehicle (0.4 mL/min), sodium nitroprusside (SNP; 3 or 5 ng/kg/min), or 5-HT (0.1 or 1 ng/kg/min). NA or 5-HT (1 ng/kg/min) were also infused with the selective 5-HT2 receptor antagonist ritanserin (500 ng/kg/min). Angiotensin II (Ang II; 0.03 to 0.3 ng/kg/min) was given as a vasoconstrictor control (n = 6). Vasoconstriction to exogenous NA was significantly enhanced by 5-HT (1 ng/kg/min; p < 0.05) in one group of subjects, but this could not be reproduced in a second group. In contrast, the vasoconstrictor responses to endogenous NA remained unaffected by 5-HT. SNP caused the same degree of vasodilation as 5-HT, and was followed by a similar response to NA. Ritanserin did not alter the vasoconstriction to infused NA, nor vasoconstriction to infused NA when combined with 5-HT. The vasoconstrictor response to Ang II was not influenced by 5-HT (0.1 ng/kg/min). Apparently, a synergistic effect between 5-HT and NA in the periphery involves a nonspecific mechanism. The latter seems to be confined to infused NA. The precise role of the 5-HT2 receptor in this interaction could not be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
Bruning
T A
TA
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Chang
P C
PC
Blauw
G J
GJ
Vermeij
P
P
Van Zwieten
P A
PA
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology*; D010991:Plethysmography; D011985:Receptors, Serotonin / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D011985:Receptors, Serotonin; D000804:Angiotensin II; D016713:Ritanserin; D009599:Nitroprusside; D012701:Serotonin; D009638:Norepinephrine; D014439:Tyramine