5-Hydroxytryptamine-induced vasodilator responses in the hindquarters of the anaesthetized rat, involve β2-adrenoceptors

Abstract

These studies were conducted to examine the role of the vasoactive mediators nitric oxide (NO) and adrenaline (epinephrine) in the serotonin (5-hydroxytryptamine; 5-HT)-induced vasodilator response in the hindquarter vascular bed of anaesthetized rats. Intra-arterial administration of doses of 5-HT in the range 0.12-25 ng kg(-1) produced a dose-independent vasodilator effect in the hindquarters. The selective 5-HT(1D/1B) receptor agonist, L-694,247 at intra-arterial doses of 0.0012-1000 ng kg(-1), as well as adrenaline (at doses of 0.05-50 ng kg(-1) i.a.), mimicked the dose-independent vasodilator effect induced by intra-arterial administration of 5-HT. Intravenous pre-treatment with the selective beta2-receptor antagonist ICI 118,551 (0.5 mg kg(-1)) blocked the vasodilator effect of 5-HT, adrenaline and L-694,247. Additionally, the inhibitor of NO synthase NG-nitro-L-arginine (L-NAME) (at a dose of 10 mg kg(-1) i.v.) blocked the vasodilator action of acetylcholine 300-3000 ng kg(-1)) but did not modify 5-HT-induced vasodilatation. The vasodilator effect produced by intra-arterial administration of 5-HT in the hindquarters was significantly inhibited both 30 min after denervation of the lumbar sympathetic chains and 1 h after bilateral adrenalectomy. Our data suggest that in the in-situ autoperfused hindquarters of the rat 5-HT-induced vasodilatation is mediated by a local 5-HT(1D) or 5-HT(1D/1B) activation, which in turn mediates the adrenal release of adrenaline, which then produces beta2-activation and vasodilatation.

<i>m</i>-CPP, a 5-HT_2C Receptor Agonist That Modifies the Perfusion Pressure of the Hindquarter Vascular Bed of Anesthetized Rat

“…3). This compound did not affect the mean blood pressure of the ani- mals but, as has been previously reported by us [17], it did inhibit the vasodilator effect of adrenaline (results not shown).…”

“…results]. Accordingly, in the present work we studied the 5-HT receptors responsible for these actions and whether the local release of NA, as shown by us previously for selective 5-HT and 5-HT 1D agonists [17], contributes to the vasodilator action of m-CPP in the hindquarters or even if this vasodilator activity is not mediated by 5-HT receptor activation.…”

5-Hydroxytryptamine Receptors as Targets for Drug Therapies of Vascular-Related Diseases

“…It has been suggested that local 5-HT 1B/1D activation in the sympathetic nervous system stimulates the release of adrenaline, which then can cause relaxation of vascular smooth muscle mediated by β 2 -adrenoceptor stimulation. 27) Additionally, chronic infusion of 5-HT produced a persistent fall in blood pressure in both deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham normotensive rats, which was contrary to expectations. 28) It has been suggested that 5-HT 1B (also 5-HT 2B and 5-HT 7 ) receptors may be involved in the dilation of peripheral arteries.…”

“…25) Intra-arterial infusion of 5-HT or the selective 5-HT 1B/1D receptor agonist L-694247 was reported to produce vasodilation in the hindquarters of anaesthetized rats. 27) These effects may be explained by endotheliumdependent vasodilation. However, the NO synthase inhibitor N(G)-nitro-L-arginine (L-NAME) did not block while the selective β 2 -adrenoceptor antagonist ICI 118551 and bilateral adrenalectomy did block the vasodilation induced by the 5-HT infusion.…”

Serotonin and Blood Pressure Regulation

“…We share here but a few examples. Calama et al (2003Calama et al ( , 2005 raise the interesting possibility that ␤ 2 adrenergic receptors are the effectors of 5-HTinduced vasodilation in the rat hindquarters, connecting 5-HT to the adrenal medulla (epinephrine release? ), because 5-HT itself does not have appreciable affinity for ␤-adrenergic receptors.…”