Carotid haemodynamics in pigs during infusions of 8-OH-DPAT: reduction in arteriovenous shunting is mediated by 5-HT1-like receptors.
1. The effects of intracarotid infusions of 8-hydroxy-2-[di-n-propyl-amino]-tetralin (8-OH-DPAT) on heart rate, blood pressure and carotid blood flow and its distribution were studied in anaesthetized pigs by use of radioactive microspheres of 15 microns diameter. 2. Control experiments with physiological saline showed that systemic and carotid haemodynamics remain essentially unchanged during the experimental period. In contrast to results obtained in rat, cat and dog experiments, 8-OH-DPAT did not decrease arterial blood pressure. 3. 8-OH-DPAT, which has a high affinity and is selective for the 5-HT1A recognition site, caused a dose-related decrease in arteriovenous anastomotic (non-nutrient) blood flow, resulting in a decrease in carotid blood flow. At the highest dose used, a small increase in arteriolar (nutrient) blood flow was observed. 4. The decrease in arteriovenous anastomotic and carotid blood flow induced by 8-OH-DPAT was not significantly modified by pretreatment with the 5-HT2 receptor antagonist ketanserin (0.5 mg kg-1), but was markedly reduced by pretreatment with methiothepin (1 mg kg-1), which blocks both the 5-HT1-like and 5-HT2 receptors. 5. It is concluded that the effects of 8-OH-DPAT on arteriovenous anastomotic blood flow are mediated by 5-HT1-like receptors. These receptors, however, cannot yet be classified as belonging to 5-HT1A receptor subtype. Since a number of antimigraine drugs reduce arteriovenous shunting, it is tempting to suggest that 8-OH-DPAT may have similar clinical efficacy.
Bom
A H
AH
Department of Pharmocology, Erasmus University Rotterdam, The Netherlands.
Verdouw
P D
PD
Saxena
P R
PR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007261:Infusions, Intra-Arterial; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D008863:Microspheres; D009281:Naphthalenes / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000502:physiology*; D013552:Swine; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin