The Inhibition by Glucagon of the Vasoconstrictor Actions of Noradrenaline, Angiotensin and Vasopressin on the Hepatic Arterial Vascular Bed of the Dog

Abstract

I The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intraarterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 gg, i.a.) caused a transient significant fall in HAVR of 19.9 + 3.2%, and infusions of 25 tg/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 + 4.2%. 4 After single injections of 100 gg glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0,g/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intraarterial infusions of 25 gg/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.

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

“…The consequent initial rise in calculated HAVR, indicating vasoconstriction, and the subsequent fall in calculated HAVR, indicating vasodilatation, were related to the dose of noradrenaline injected ( Figure 2) until doses in excess of 10 or 50 jig in different experiments were injected, when no secondary effect was apparent. The Richardson & Withrington, 1976a). The maximum secondary reduction in HAVR to noradrenaline of 16.0 + 2.4% was however significantly smaller than the maximum response to isoprenaline of 38.6 + 2.9% (P< 0.001) where maximum responses to both agents were established in the same 8 preparations.…”

“…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.…”

A COMPARISON OF THE EFFECTS OF BRADYKININ, 5‐HYDROXYTRYPTAMINE AND HISTAMINE ON THE HEPATIC ARTERIAL AND PORTAL VENOUS VASCULAR BEDS OF THE DOG: HISTAMINE H1 AND H2‐RECEPTOR POPULATIONS

“…These preparations have been described previously (arterial: Richardson & Withrington, 1976b;portal: Richardson & Withrington, 1977) (Bayliss, 1902;Folkow, 1964) are, in these preparations, negligible compared with the drug-induced changes in HAVR, whether vasoconstrictor (Richardson & Withrington, 1976a) or vasodilator (Richardson & Withrington, 1976b) (Levophed, Winthrop; mol. wt. of base = 169.0).…”

“…Vasopressin, whilst causing hepatic artery of the anaesthetized dog cause dose-profound dose-dependent vasoconstriction of the dependent hepatic arterial vasoconstriction (Andrews, hepatic arterial vascular bed (Richardson & Hecker, Maegraith & Ritchie, 1955;Richardson & Withrington, 1976a) has little effect on the resistance Withrington, 1976a); when administered by injection sites of the portal system except with very high doses into the hepatic portal vein they cause portal venous when it causes a reduction in portal vascular vasoconstriction although the responses to angio-resistance (Richardson & Withrington, 1977). tensin show marked tachyphylaxis (Richardson & Quantitative and qualitative differences in the responses of the hepatic arterial and portal vascular beds to naturally-occurring substances are therefore evident.…”

Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II

“…Sasaki et al (1985) reported that angiotensin II increased the concentration of arteriallyinfused krypton -81 m in both primary and metastatic liver tumours. This implies an increase in tumour blood flow relative to total hepatic arterial flow, but, as angiotensin II reduces hepatic arterial flow in the normal liver (Richardson & Witherington, 1976) All patients were studied at the time of placement of infusion catheters for regional delivery of chemotherapeutic drug to liver tumour. This study was approved by the hospital ethical committee, and all patients gave informed consent.…”