THE VASODILATOR ACTIONS OF ISOPRENALINE, HISTAMINE, PROSTAGLANDIN E₂, GLUCAGON AND SECRETIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG

Abstract

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 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. 5Comparisons on a molar basis showed that secretin and prostaglandin E2 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 ROLE OF Β‐ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE

“…The complete dose-response curve creases in the to isoprenaline on this preparation has been published al doses of previously (Richardson & Withrington, 1976d (Figure 4). These responses and their time courses )st of the dosewere similar to the responses to isoprenaline tation due to (Richardson & Withrington, 1976d).…”

“…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.…”

“…and the hepatic artery cannulated and perfused with blood from a femoral artery. The hepatic arterial mean blood flow and mean perfusion pressure were monitored continuously as described previously (Richardson & Withrington, 1976d). In addition, the systemic arterial blood pressure, heart rate, and inferior vena cava pressure were recorded continuously, to monitor the possible systemic effects resulting from large doses of locally administered drugs which may survive passage through the liver and pulmonary vascular bed to enter the systemic circulation.…”

“…No subsequent vasoconstrictor responses were observed after the intraarterial injection of isoprenaline in the present experiments; the maximum reduction in the calculated HAVR to isoprenaline was 39.1 + 2.0% (n = 9). The effects of maximal vasodilator doses of isoprenaline have been described previously (Richardson & Withrington, 1976d).…”

“…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.…”