The Effects of Glucagon, Secretin, Pancreozymin and Pentagastrin on the Hepatic Arterial Vascular Bed of the Dog

Abstract

1The sympathetically-innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were monitored continuously and the hepatic arterial vascular resistance (HAVR) calculated from these measurements. 2 Commercial preparations of secretin, pancreozymin, glucagon and pentagastrin were administered by intra-arterial (i.a.) injection and infusion. 3 Secretin and pancreozymin by injection caused dose-dependent hepatic arterial vasodilatation, and on a molar basis were both more potent than glucagon or pentagastrin. 4 Intra-arterial infusions of secretin and pancreozymin caused hepatic arterial vasodilatation at calculated blood concentrations close to those measured under physiological conditions by other investigators. The vasodilatation was of the same duration as that of the hormone infusions. 5Pentagastrin by i.a. injection caused dose-dependent hepatic arterial vasodilatation; by i.a. infusion, vasodilatation occurred but there was marked 'escape' from the effects during the continued infusion.6 As reported previously, glucagon by injection caused dose-dependent hepatic arterial vasodilatation of long duration; by infusion, glucagon caused vasodilatation that persisted after the cessation of the infusion. 7 Glucagon infused i.a., inhibited the vasoconstrictor effects of i.a. noradrenaline, over the same range of infusions that caused hepatic arterial vasodilatation. 8 Secretin or pancreozymin did not antagonize the effects of noradrenaline on the hepatic arterial vascular bed at any doses used. 9 Pentagastrin did not antagonize the vasoconstrictor effect of noradrenaline whether hepatic arterial vasodilatation resulted from the pentagastrin infusion, or not. 10 These results are discussed with respect to the possible control of the hepatic arterial vascular bed by gastrointestinal hormones.

The ROLE OF Β‐ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE

“…The use of the sympathetically-innervated arterial vascular bed of the dog's liver for the quantitative study of the effects of vasodilator hormones has previously been reported from this laboratory, and the relative molar potencies of a range of naturallyoccurring and synthetic vasodilator agents established (Richardson & Withrington, 1976c, d;1977a). In the present experiments, this preparation has been used to study the vascular effects of noradrenaline and adrenaline, injected intra-arterially, comparing these with the synthetic a-and P-adrenoceptor agonists, phenylephrine and isoprenaline respectively.…”

“…Whilst it may be that the hepatic arterial vasodilatation is a secondary effect of /3-adrenoceptor-mediated stimulation of liver metabolism, the two effects, both mediated by /3-adrenoceptors may well have distinct receptor sites. It seems probable that the vasodilator action of adrenaline is of physiological importance in ensuring an adequate blood flow to the hepatic parenchyma in states of stimulated liver metabolism; in this context, the study of the effects of intra-arterial infusions of catecholamines which may more closely mimic the physiological release of suprarenal medullary catecholamines than acute injections, may be of importance, as may the possible interactions between adrenaline and other hormones such as glucagon (Richardson & Withrington, 1976a, c;1977a).…”

“…The technique used in these experiments was the same as that reported previously (Richardson & Withrington, 1976d;1977a) and only brief details of the preparation are given here.…”

“…However, quantitative comparisons of the potencies of the vasoconstrictor agents before and after phentolamine is complicated by the alteration in the control hepatic arterial vascular resistance caused by the administration of phentolamine (Hanson, 1973). It is not possible to assess the influence of aadrenoceptor blockade upon the vasodilator responses to isoprenaline or the secondary falls in HAVR due to adrenaline and noradrenaline because the vasodilator action of phentolamine reduced the vascular tone necessary for the quantitative evaluation of vasodilatation in this bed (Richardson & Withrington, 1976d;1977a).…”

“…In order to demonstrate vasodilatation quantitatively in this vascular bed, it is necessary to retain the sympathetic innervation intact (Richardson & Withrington, 1976d;1977a); if the periarterial nerves accompanying the hepatic artery are sectioned, catecholamines injected intra-arterially cause only vasoconstriction (Richardson & Withrington, 1976a and unpublished observations); similarly, the administration of a-adrenoceptor antagonist drugs may reduce the hepatic arterial vasoconstrictor tone which is necessary for the quantitative examination of vasodilator responses.…”