Investigation of the role of 5‐HT<sub>1B</sub> and 5‐HT<sub>1D</sub> receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses

Vries, Peter de; Willems, Edwin; Heiligers, Jan P.C.; Villalón, Carlos M.; Saxena, Pramod R.

doi:10.1038/sj.bjp.0702572

Cited by 45 publications

(33 citation statements)

References 36 publications

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“…The vasoconstrictor effect increases the resistance of carotid arteries and reduces cerebral blood flow (CBF) (Feniuk et al, 1989;den Boer et al, 1991;De Vries et al, 1999b). Cerebral vessels are assumed to dilate during migraine headache and CBF changes during migraine attacks, as reported by Olesen et al (1990).…”

Section: Introductionmentioning

confidence: 96%

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Okazawa

Tsuchida

Pagani

et al. 2005

J Cereb Blood Flow Metab

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To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT 1B/1D ) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H 2 15 O to analyze CBF and arterial-to-capillary blood volume (V 0 ) images using the threeweighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V 0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V 0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V 0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V 0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V 0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V 0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction.

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Section: Introductionmentioning

confidence: 96%

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Okazawa

Tsuchida

Pagani

et al. 2005

J Cereb Blood Flow Metab

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“…The pigs had been used in in vivo experiments studying the effects of ␣-adrenoceptor and serotonin receptor agonists and antagonists under pentobarbital (600 mg IV) anesthesia. 15 The ethics committee of Erasmus University Rotterdam dealing with the use of animals for scientific experiments approved the protocol for this investigation. Hearts were explanted at the end of the experiment, and the coronary arteries were removed immediately and handled in the same way as HCAs.…”

Section: Tissue Collectionmentioning

confidence: 99%

Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade

et al. 2001

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Abstract-ACE inhibitors block B 2 receptor desensitization, thereby potentiating bradykinin beyond blocking its hydrolysis. Angiotensin (Ang)-(1-7) also acts as an ACE inhibitor and, in addition, may stimulate bradykinin release via angiotensin II type 2 receptors. In this study we compared the bradykinin-potentiating effects of Ang-(1-7), quinaprilat, and captopril. Porcine coronary arteries, obtained from 32 pigs, were mounted in organ baths, preconstricted with prostaglandin F 2␣ , and exposed to quinaprilat, captopril, Ang-(1-7), and/or bradykinin. Bradykinin induced complete relaxation (pEC 50 ϭ8.11Ϯ0.07, meanϮSEM), whereas quinaprilat, captopril, and Ang-(1-7) alone were without effect. Quinaprilat shifted the bradykinin curve to the left in a biphasic manner: a 5-fold shift at concentrations that specifically block the C-domain (0.1 to 1 nmol/L) and a 10-fold shift at concentrations that block both domains. Captopril and Ang-(1-7) monophasically shifted the bradykinin curve to the left, by a factor of 10 and 5, respectively. A 5-fold shift was also observed when Ang-(1-7) was combined with 0.1 nmol/L quinaprilat. Repeated exposure of porcine coronary arteries to 0.1 mol/L bradykinin induced B 2 receptor desensitization. The addition of 10 mol/L quinaprilat or Ang-(1-7) to the bath, at a time when bradykinin alone was no longer able to induce relaxation, fully restored the relaxant effects of bradykinin. Angiotensin II type 1 or 2 receptor blockade did not affect any of the observed effects of Ang-(1-7). In conclusion, Ang-(1-7), like quinaprilat and captopril, potentiates bradykinin by acting as an ACE inhibitor. Bradykinin potentiation is maximal when both the ACE C-and N-terminal domains are inhibited. The inhibitory effects of Ang-(1-7) are limited to the ACE C-domain, raising the possibility that Ang-(1-7) synergistically increases the blood pressure-lowering effects of N-domain-specific ACE inhibitors. is a heptapeptide that is formed endogenously from both Ang I and Ang II. 1 In rats and dogs, Ang-(1-7) exerts direct vasodilatory effects via nonangiotensin II type 1 (AT 1 ), non-angiotensin II type 2 (AT 2 ) receptors, possibly by stimulating bradykinin and NO release. 1,2 In contrast, in humans or pigs, no direct vasodilatory effects of Ang-(1-7) were observed, 3-7 although Ang-(1-7) did antagonize the pressor effects of Ang II, suggesting that it may cause vasodilation indirectly, by acting as an AT 1 receptor antagonist. 5,6 In addition, Ang-(1-7) potentiates bradykinin, either via an AT 2 receptor-dependent mechanism or through inhibition of ACE. 3,5,8 The latter effect is not necessarily based on blockade of bradykinin hydrolysis, because recent studies have shown that ACE inhibitors, including Ang-(1-7), potentiate bradykinin by inhibiting desensitization of its receptor. 9 -11 Somatic ACE has 2 homologous domains, each containing an active center. According to their position (N-or C-terminal), these domains are designated as the N-or C-domain, respectively. Interestingly, Ang-(1-7) inhibits t...

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“…SB224289, but not BRL15572 antagonises the effects of sumatriptan (Fig. 2) [12]. Despite the fact that our recent investigation revealed that BRL15572, has a low affinity for the porcine 5-HT 1D receptor in contrast to the human 5-HT 1D receptor [13], it is obvious that the 5-HT 1B receptor mediates carotid vasoconstrictor response.…”

mentioning

confidence: 81%

Success and failure of triptans

Saxena¹,

Tfelt‐Hansen

2001

J Headache Pain

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Investigation of the role of 5‐HT_1B and 5‐HT_1D receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses

Cited by 45 publications

References 36 publications

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade

Success and failure of triptans

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Investigation of the role of 5‐HT1B and 5‐HT1D receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses

Cited by 45 publications

References 36 publications

Effects of 5-HT1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Effects of 5-HT1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Bradykinin Potentiation by Angiotensin-(1-7) and ACE Inhibitors Correlates With ACE C- and N-Domain Blockade

Success and failure of triptans

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Product

Resources

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Investigation of the role of 5‐HT_1B and 5‐HT_1D receptors in the sumatriptan‐induced constriction of porcine carotid arteriovenous anastomoses

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation