Hepatic Arterial Vascular Resistance Research Articles

Glucagon inhibition of hepatic arterial responses to hepatic nerve stimulation.

The hepatic arterial vascular bed of the chloaralose-urethan-anesthetized dog was perfused with blood from a cannulated femoral artery. Hepatic arterial blood flow and perfusion pressure were measured. The hepatic periarterial postganglionic sympathetic nerves were stimulated supramaximally at 0.1, 0.5, 1, 2, 5, 10, and 20 Hz; this caused frequency-dependent rises in the calculated hepatic arterial vascular resistance at all frequencies above the threshold of 0.1 or 0.5 Hz. Glucagon was infused intra-arterially in dosese from 0.25 to 10 microgram/min; glucagon antagonized both the vasoconstrictor effects of hepatic nerve stimulation and of intra-arterial injections of norepinephrine. The degree of antagonism of these responses was significantly correlated with the calculated hepatic arterial glucagon concentration. It is possible that glucagon released physiologically in stress and hypoglycemia may protect the hepatic arterial vasculature from the effects of increased sympathetic discharge.

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

The sympathetically‐innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements. Intra‐arterial injections of phenylephrine caused dose‐dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses. Intra‐arterial injections of isoprenaline caused only dose‐dependent reductions in HAVR at doses above threshold. Intra‐arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR. Intra‐arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation. On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine. The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline (P < 0.001). Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra‐arterial adrenaline and noradrenaline. Propranolol did not modify the vasoconstrictor responses to phenylephrine. Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of β‐adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant. After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline. Since the β‐adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the β2‐type. The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose‐response curves being shifted to the right. The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally‐occurring catecholamines.

The effects of glucagon, secretin, pancreozymin and pentagastrin on the hepatic arterial vascular bed of the dog.

1 The 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, pancroezymin, 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. 5 Pentagastrin 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 vasoconstricter 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 VASODILATOR ACTIONS OF ISOPRENALINE, HISTAMINE, PROSTAGLANDIN E2, GLUCAGON AND SECRETIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG

The sympathetically-innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were measured continuously, and the hepatic arterial vascular resistance calculated. The preparation provided a means of assessing hepatic arterial vasodilatation quantitatively. 2 Isoprenaline, histamine, prostaglandin E2, glucagon and secretin were injected intra-arterially and all evoked dose-dependent vasodilatation of the hepatic arterial vascular bed. 3 The maximum reduction in the calculated hepatic arterial vascular resistance of 37-38% was the same for each of the five substances. 4 Comparisons on a weight basis revealed that prostaglandin E2 was the most potent, followed in potency order by secretin, isoprenaline, histamine and glucagon. 5 Comparisons on a molar basis showed that secretin and prostaglandin E3 were intrinsically considerably more potent than isoprenaline, histamine or glucagon. 6 The onset of the vasodilatator responses to secretin, isoprenaline, histamine and prostaglandin E2, was rapid, and the duration of their actions was brief. 7 The onset of the vasodilator effects of glucagon was slow and its duration of action very prolonged. 8 The implications of these observations with respect to the physiological control of the hepatic arterial vascular bed of the dog are discussed.

The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog.

1 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 intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug 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 mug/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 intra-arterial infusions of 25 mug/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.