The actions of two sensory neuropeptides, substance P and calcitonin gene-related peptide, on the canine hepatic arterial and portal vascular beds.
1. The two peptides, calcitonin gene-related peptide (CGRP) and substance P (SP) were administered individually as bolus injections into the separately perfused hepatic arterial and portal vascular beds of the anaesthetized dog to assess their actions and relative molar potencies at these sites. 2. CGRP caused an immediate dose-related increase in hepatic arterial flow when injected close-arterially, reflecting a fall in resistance. This vasodilator effect was slightly increased by the prior administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551. 3. On a molar basis, CGRP was more potent as an hepatic arterial vasodilator than the non-selective beta-adrenoceptor agonist, isoprenaline (Iso). 4. Intra-portal injection of CGRP also evoked hepatic arterial vasodilatation unaccompanied by other cardiovascular changes. 5. CGRP in doses up to 10 nmol had no effect on portal vascular resistance when administered intra-portally. 6. SP evoked a rapid, dose-related increase in hepatic arterial flow when injected intra-arterially. The molar ED50 for this hepatic vasodilatation was 40.2 fmol, significantly less than the ED50 for either CGRP or Iso. SP was the most potent hepatic arterial vasodilator yet examined. The vasodilator effect of SP was slightly potentiated by prior beta 2-adrenoceptor blockade. 7. SP caused hepatic arterial vasodilatation when administered by intra-portal injection; its absolute and relative potency was much reduced. 8. SP when injected intra-portally caused a graded increase in hepatic portal inflow resistance. The molar potency for this portal vasoconstriction was significantly greater than that for noradrenaline (NA); however, the maximum increase in portal resistance was significantly less to SP than to NA.9. In view of the location of the peptides CGRP and SP within the afferent innervation of the liver, it is proposed that they play an important function in controlling the hepatic microvasculature in response to sensory stimuli, particularly those arising from changes in portal blood composition secondary to change in metabolic activity within the gastrointestinal tract (GIT).10. Since the peptides are released from the GIT into the hepatic portal inflow, they may modify hepatic arterial blood flow, the extent of which is related to events within the GIT.
Withrington
P G
PG
Department of Pharmacology, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006499:Hepatic Artery / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008102:Liver Circulation / Q000187:drug effects*; D011168:Portal System / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013373:Substance P; C026777:ICI 118551; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol