Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery

Abstract

. Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery. Am J Physiol Heart Circ Physiol 284: H719-H726, 2003; 10.1152/ajpheart.00345.2002.-The modulation of serotonin (5-HT1B/1D) receptor-induced vascular contractility by histamine and U-46619 was compared in the rabbit basilar artery and saphenous vein. In the saphenous vein, histamine (5 ϫ 10 Ϫ7 M) significantly increased the potency (from pEC50 of 6.0 to 6.8) and efficacy (from 52.3% to 88.2%) of sumatriptan. Likewise, U-46619 (5 ϫ 10 Ϫ9 M) also increased the potency (from pEC50 of 5.9 to 6.6) and efficacy (from 51.8% to 92.1%) of sumatriptan in the saphenous vein. In contrast, equieffective concentrations of histamine (10 Ϫ7 M) and U-46619 (3 ϫ 10 Ϫ9 M) failed to amplify contraction to sumatriptan in the basilar artery. Contraction to sumatriptan was inhibited by nitrendipine (10 Ϫ7 M) in the basilar artery but not in the saphenous vein, suggesting that different contractile signaling mechanisms are operating in these tissues. Furthermore, U-46619-and thrombin-induced contractility in the basilar artery were also not amplified by histamine, suggesting that lack of amplification of contraction in the basilar artery was not restricted to sumatriptan but was rather a characteristic of this cerebral vessel. These data suggest that in the in vivo plasma milieu sumatriptan will more markedly contract the peripheral saphenous vein than the basilar artery, a cerebral blood vessel. nitrendipine; histamine; U-46619; serotonin receptors SUMATRIPTAN is an antimigraine drug (20) with a high affinity for serotonin 5-HT 1B and 5-HT 1D receptors (27). The antimigraine efficacy of sumatriptan has been attributed, in part, to its ability to activate central vascular 5-HT 1B/1D receptors (8). However, much of the information on the vascular effects of sumatriptan has been derived from studies using peripheral vascular serotonin receptors. For example, sumatriptan-induced peripheral vascular contraction has been widely studied in the rabbit saphenous vein (9), femoral artery (4), mesenteric artery (5), and iliac artery (36). Because the cardiovascular liabilities of sumatriptan may be related to its ability to constrict coronary arteries (23), sumatriptan has also been studied in coronary arteries from dogs (21) and humans (1). In contrast, the cerebral vascular effects of sumatriptan have been less extensively studied (3,16,17).Modest increases in vascular tone with threshold concentrations of vascular contractile agonists such as prostaglandin, angiotensin, histamine, endothelin, or adrenergic agonists are known to increase sumatriptaninduced vascular contractility (35). Whereas this amplifying effect is well established in peripheral blood vessels (7,9,21,22

5-Hydroxytryptamine1B Receptor-Mediated Contraction of Rabbit Saphenous Vein and Basilar Artery: Role of Vascular Endothelium

“…Male New Zealand White rabbits (2.0 -3.0 kg) (Harlan, Indianapolis, IN) were sacrificed by injection of sodium pentobarbital (65-100 mg/kg) into the ear vein according to animal use protocols approved by the Lilly Animal Care and Use Committee. The saphenous vein and/or basilar artery was dissected free of connective tissue, cannulated with 99.9% platinum wire (32-gauge for saphenous vein; 36-gauge for basilar artery) in petri dishes containing Krebs' bicarbonate buffer (Bhattacharya et al, 2003). When appropriate, tissues were denuded of vascular endothelium by rotating the platinum wires along the luminal surface of the blood vessels.…”

“…Tissue bath solutions were maintained at 37°C and aerated with 95% O 2 and 5% CO 2 (pH 7.4). An initial optimum force of 4 and 0.5 g was applied to the rabbit saphenous vein and basilar artery, respectively, resulting in baseline tensions of 1 and 0.25 to 0.30 g in the two tissues (Bhattacharya et al, 2003). Isometric contractions were recorded as changes in grams of force as measured with Sensotec transducers coupled to MP100 data acquisition software (BIOPAC Systems, Inc., Santa Barbara, CA).…”

“…The rabbit saphenous vein and basilar artery are convenient in vitro models for studying vascular contractility as surrogates for human peripheral and central vasculature (Cohen et al, 1997;Bhattacharya et al, 2003). Furthermore, mRNA for both 5-HT 1B (high-density) and 5-HT 1D (low-density) receptors are present in the saphenous vein (Wurch et al, 1997) and in cerebral vessels (Bouchelet et al, 1996), raising the possibility that both receptors may play a role in contractility in these tissues to varying degrees.…”

“…The rabbit basilar artery has not been characterized for the sumatriptansensitive receptor(s), although 5-HT 1B and 5-HT 1D receptors are thought to contribute to rabbit basilar artery contraction (Parsons et al, 1998). Interestingly, sumatriptan displayed distinct differences in amplification mechanisms between saphenous vein and basilar artery (Bhattacharya et al, 2003), indicating the possibility that different receptor subtypes may mediate contraction in the two tissues.…”

Serotonin (5-HT) in Veins: Not All in Vain

“…Neuropeptide Y potentiates 5-HT-induced contraction in porcine coronary artery, and 5-HT sensitivity is increased by phenylephrine in rabbit femoral artery (Tsurumaki et al, 2006). In rabbit saphenous vein, histamine and the thromboxane A 2 agonist increased the potency and efficacy of the 5-HT 1B/1D agonist sumatriptan, an effect that was not observed in basilar artery (Bhattacharya et al, 2003).…”