Effect of substance P on CCK- or VIP-induced choleresis in anesthetized dogs.

10 anesthetized dogs were provided with acute common bile duct fistulas and the gallbladder was excluded. Hepatic bile output and biliary content of sodium, potassium and amylase were studied. 6 caval infusions were administered of CCK, 0.3 Ivy U.kg-1.min-1, with a superimposed infusion of SP, 20 ng.kg-1.min-1. 7 caval infusions were given of VIP, 50 ng.kg-1.min-1, with a superimposed infusion of SP, 20 ng. kg-1.min-1. CCK increased bile output and biliary content of sodium, potassium and amylase by 78-110%. The corresponding increase induced by VIP was 55-85%. Biliary pH was not influenced. SP abolished the effects of both CCK and VIP. It is suggested that all peptides studied influenced canalicular bile secretion by changing the electrolyte excretion.     

Anticholeretic effect of substance P in anesthetized dogs

Nine anesthetized dogs were provided with acute common duct fistulas after exclusion of the gallbladder. Synthetic Substance P was administered as caval infusions in a dosage of 0.5-20 ng x kg-1 x min-1, duration 10 min. The output of hepatic bile, sodium and amylase decreased during infusion by 40-52 per cent at the highest doses. After termination of infusion all 3 parameters increased by 19-60 per cent above the basal level. The biliary concentration of sodium was constant, while that of amylase increased during infusion. The responses were dose-related. The anticholeresis induced by substance P might be due to inhibition of the canalicular bile fraction, which presumably is mediated by active sodium transport and independent of bile salt excretion.     

Anticholeretic effect of somatostatin in anesthetized dogs

Somatostatin, 0.2-1.0 βg. kg^-l min^-1, was administered i.v. in 5 anesthetized dogs. Following 9-min infusions, hepatic bile output was found to decrease by approximately 50% after a latency of 6 min. The mode of action suggests that somatostatin inhibits hormone-induced bile output.     

Angiotensin II infusion during β-adrenergic stimulation by isoproterenol. Effects on hepatic,splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1–0.2 μg kg^-1 min^-1 i.v.) during high β-adrenergic activity by a continuous isoproterenol infusion (0.2–0.3 μg kg^-1 min^-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic-technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 ± 3 mmHg and the stroke volume by 17 ± 6 %. Concomitantly, the hepatic and splenic blood volumes declined by 29 ± 4 and 14 ± 6 ml, respectively, and the LV end-diastolic segment length increased by 3 ± 1 %. The flow through the inferior caval vein increased by 39 ± 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.,     

Systemic and centrally mediated angiotensin II effects in the horse

The primary aim of the study was to evaluate the potential value of intravenous (i. v.) infusion of angiotensin II (AII) for phonocardiographic differential diagnosis of equine valvular insufficiency. Ten-minute AII infusions at 4.5–33 pmol kg^-1 min^-1 induced clear-cut dose-dependent rises in systemic arterial blood pressure (aBP), whereas the pulmonary aBP remained largely unaffected. It implies that i. v.infusion of All at about 10 pmol kg^-1 min^-1 could be a valuable tool for the acoustic differentiation between mitral and tricuspid valvular dysfunction in the horse. The infusion at, and above 9 pmol kg^-1 min^-1 caused increased heart rate. This chronotrophic effect was not strictly dose-dependent and exhibited significant tachyphylaxis. Angiotensin II administration at, or above 9 pmol kg^-1 min^-1 was needed to induce an urge to drink, suggesting that angiotensin-induced thirst does not appear in the euhydrated horse until the octapeptide reaches supraphysiological blood concentration. Determinations of plasma aldosterone concentration (PA) revealed comparatively high morning control values (269 ± 46 pmol^-1).Three consecutive AII infusions with 10-min intervals and at increasing dosages caused a cumulative, almost fourfold elevation of PA.The PA pattern indicated that AII-induced hypersecretion of aldosterone continued for several minutes after the end of the infusions, but also showed that the metabolic clearance of the hormone took precedency of the secretion within 20 min post-infusion. In two of the horses a fall in PA occurred during a fourth, final infusion, indicating that in these instances the previous AII administration had impoverished the store of aldosterone available for release from the adrenal cortex.     

Calciuresis elicited by spontaneous rehydration in dehydrated sheep

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg^-1 min^-1) were investigated in conscious dogs. In addition, the disappearance of ET-l in arterial and central venous plasma after an infusion of 10 ng kg^-1 min^-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg^-1 min^-1) and angiotensin II (AII, 2, 5, and 10 ng kg^-1 min^-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 ± 0.3 to 243 ± 23 pg ml^-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 ± 4 to 29 ± 3 ml min^-1 and 87 ± 16 to 71 ± 14 μmol min^-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t_½ was 1.1 ± 0.1 min. Vasopressin increased arterial blood pressure (107 ± 4 to 136 ± 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin – in contrast to angiotensin II – is able to increase the plasma concentration of ET-1. The latter may suggest that ET-1 is involved in the prolonged pressor action of AVP observed.     

Increased myometrial blood flow evoked by substance P

Substance P (SP), a vasoactive neuropeptide, has recently been demonstrated in the female genital tract. In the present paper we have investigated the relationship between substance P (0, 0.065, 6.5, 650 pmol · min^–1 · kg^–1) administered by close intraarterial infusions, and myometrial blood flow (MBF). The MBF was measured by the¹³³Xe washout technique in ten non-pregnant, estrogen pretreated, female rabbits anaesthetized with sodium pentobarbitone. SP increased MBF in a dose-dependent fashion. This effect was not influenced by cholinergic, adrenergic or enkephalinergic blocking agents, indicating a direct effect of substance P on vascular smooth muscle. Substance P may therefore play a physiological role in the local nervous control of myometrial blood flow.     

Effect of C-peptide administration on whole body glucose utilization in STZ-induced diabetic rats

Recent studies suggest that C-peptide stimulates glucose transport in isolated skeletal muscle. In order to determine the effect of C-peptide on whole body glucose utilization, streptozotocin (60 mg kg^-1) (STZ)-induced diabetic and normal rats were studied using the euglycaemic clamp procedure and continuous infusion of somatostatin (1.0 μg kg^-1 min^-1) in pentobarbital-anaesthetized rats. Plasma insulin levels during the 6.0- and 30.0-mU kg^-1 min^-1 insulin infusions rose to 70–90 μU mL^-1 and 500–700 μU mL^-1, respectively. Blood glucose concentrations were clamped at 7.5–7.9 mmol L^-1 in the diabetic rats and at basal levels or 7.7 mmol L^-1 in the non-diabetic (normal) rats. Biosynthetic human C-peptide (0.5 nmol kg^-1 min^-1) was infused in 12 diabetic and 11 normal rats, resulting in concentrations of 26–41 nmol L^-1. The metabolic clearance rate of glucose (MCR) for the diabetic rats receiving C-peptide (12.0±1.0 mL kg^-1 min^-1) was significantly (P<0.01) higher than that in the diabetic rats given saline (6.3±0.7 mL kg^-1 min^-1) or a randomly scrambled C-peptide (7.8±1.3 mL kg^-1 min^-1) at low-dose insulin infusion but not at the high-dose insulin infusion. In normal rats C-peptide did not significantly increase the MCR for glucose. These results thus demonstrate that C-peptide has the capacity to increase glucose utilization in STZ-induced diabetic rats.     

Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pigs under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled 0₂ from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg^-1 min^-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg^-1min^-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg^-1 min^-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg^-1 min^-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.     

Effect of Substance P on Various Vascular Beds in the Dog

Using the electromagnetic flowmeter technique, the blood flow in the aorta, carotid, hepatic, superior mesenteric, renal and femoral arteries and portal vein was recorded during continuous i.v. infusion of synthetic Substance P (SP) in 8 dogs. Systemic and portal blood pressures were recorded. A significant decrease in mean arterial blood pressure was recorded at infusion of SP in the femoral vein at a rate of 2.5 ng × min^-1× kg b.w.^-1 or higher. Portal venous blood pressure increased. A rapid increase in the carotid, hepatic, mesenteric and portal blood flow was obtained at infusion rates of 1.2 ng × min^-1× kg b.w.^-1 or higher. The femoral artery responded with a late, transient increase in flow, with a return to the base level while the infusion was still in progress. The renal artery blood flow decreased slightly at low infusion rates and increased at higher. At SP infusions in the portal vein the infusion rate had to be increased to 20 ng × min^-1× kg b.w.^-1 or higher before any general vascular reactions were recorded, indicating that the liver has a high capacity for inactivating SP.     

Pancreatic secretory response to cholecystokinin-pancreozymin and caerulein in the conscious rat

1. The effects of graded intravenous doses of cholecystokinin (CCK) and caerulein on exocrine pancreatic secretion have, been assessed in conscious rats. Bile and pancreatic juice were separately returned to the duodenum between and during tests.
2. Low doses of CCK (from 417 to 3,335 ng kg^?1 h^?1) or caerulein (from 37.5 to 150 ng kg^?1 h^?1) slightly increased flow rate but increased K⁺ and HCO ₃ ^? outputs to a greater extent, without altering Cl^? output. The sum of the anion concentrations (Cl^?+HCO ₃ ^? ) stayed constant, which explains the decrease in Cl^? concentration when the HCO ₃ ^? concentration increased.
3. High doses of CCK (6,670 and 13,335 ng kg^?1 h^?1) and of caerulein (600 ng kg^?1 h^?1 strongly inhibited volume flow and outputs of all the ions, and the sum of the concentrations of anions fell.
4. Protein concentration and output increased with the same time course in response to both CCK and caerulein, i. e. course in response to both CCK and caerulein, i. e. a sustained stimulation during infusion, without any delayed inhibitory effect afterwards. The increase followed a linear dose-response relation to both CCK and caerulein. D50 was approximately 1,000 ng kg^?1 h^?1 for CCK and 95 ng kg^?1 h^?1 for caerulein. The maximal secretory rate of protein in our experiments was obtained with 300 ng kg^?1 h^?1 caerulein (20.27 mg 30 min^?1) and was almost twice that obtained with CCK (10.6 mg 30 min^?1) which suggests that the most potent agonist is a shorter derivative of CCK. Finally, both hormones decreased protein output at supramaximal levels.
5. It is concluded that both CCK and caerulein have similar effects on pancreatic secretion in the conscious rat and in other species. However, the conscious rat differs from other species in that water, HCO ₃ ^? and K⁺ secretions are stimulated by low doses of agonists. In contrast, high doses of agonists inhibited all components of secretion.

     

Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg^-1 min^-1 (arginine vasopressin) or 1 ng kg^-1 min^-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 ± 0.2 (arginine vasopressin alone) and 1.8 ± 0.3 pg kg^-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 ± 5 (oxytocin alone) and 77 ± 8 pg ml^-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 ± 2 to 15 ± 6 μmol min^-1 and from 7 ± 4 to 25 ± 13 μmol min^-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 ± 4 to 101 ± 27 μmol min^-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na⁺/K⁺ ratio by a factor of 3.7. It is concluded, that oxytocin at plasma concentrations of 70–80 pg ml^-1 has modest antidiuretic and natriuretic effects and that the combined action of arginine vasopressin oxytocin may elicit supra-additive natriuretic effects.     

The progressive pressor response to angiotensin in the rabbit

1. The threshold for any detectable rise of systemic arterial pressure during the prolonged intravenous administration of angiotensin to conscious rabbits was observed to be an infusion rate of 0·003-0·006 μg.kg^-1.min^-1.

2. At infusion rates between threshold and 0·04 μg.kg^-1.min^-1 the systemic arterial pressure rose progressively over a 3- to 7-day period to a plateau.

3. On stopping the angiotensin infusion the blood pressure fell rapidly back to its base line much faster than it rose during the infusion. The time taken to reach control values was approximately related to the duration of the infusion.

4. At infusion rates of about 0·05 μg.kg^-1.min^-1 the full rise of blood pressure developed within a few minutes, and could be sustained without change for many days. At higher rates the blood pressure diminished with time.

5. Diurnal fluctuations of blood pressure were often seen during prolonged infusions of angiotensin at low rates; and more rapid fluctuations of blood pressure over an hour or two were frequently encountered immediately after an infusion was turned off.

6. The possible role of angiotensin in producing chronic renal hypertension is discussed in the light of these observations.

     

Adrenergic influence on bile secretion—an experimental study in the cat

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h^-1 kg^-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an α-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly α-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a β-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the α-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.     

Intravenous bilirubin infusion causes vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis

To examine whether intravenous bilirubin infusion causes cholestasis and impairs liver metabolism, bile secretion and ethanol clearance were measured in 34 anaesthetized pigs before and after intravenous infusion of 0.5 μmol kg^-1 min^-1 bilirubin for 4.5 hours. Bilirubin infusion increased plasma bilirubin to 556±76 μmol l^-1 and hepatic tissue bilirubin to 3.5 ± 1.3 mmol kg tissue weight^-1. Bilirubin infusion depressed bilirubin secretion and net hepatic uptake of cholate and taurocholate, and caused a 86±6% reduction of cholate-induced bile secretion. Bilirubin caused formation of large cytoplasmic vacuoles in hepatocytes and dilatation of bile canaliculi. Ethanol clearance and secretin-dependent ductular bile secretion were unaffected by bilirubin. We conclude that intravenous infusion of unconjugated bilirubin causes accumulation of bilirubin in the liver, vacuolization of the hepatocyte cytoplasm and canalicular but not ductular cholestasis. The canalicular cholestasis is not due to impaired hepatic mitochondrial energy metabolism, but may be due to inhibition of a common pathway for lipid, bilirubin and bile salt secretion from hepatocytes.     

Inhibitory effect of endothelin on renin release in dog kidneys

To investigate the effect of endothelin on renin release, experiments were performed in barbiturate-anaesthetized dogs with denervated kidneys. Intrarenal infusion of endothelin (1 ng min^-1kg^-1body wt) reduced renal blood flow (RBF) from 145 ± 10 ml min^-1to 98 ± 9 ml min^-1without altering renin release (1 ± 1 μg angiotensin I (AI) min^-1). Renin release was then increased either by renal arterial constriction or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 ± 20 μg AI min^-1in six dogs and fell significantly to 24 ± 6 μg AI min^-1during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition of β-adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 ± 2 μg AI min^-1to 38 ± 12 μg AI min^-1in six dogs. Subsequent intrarenal endothelin infusion (1 ng min^-1kg^-1body wt) during maintained ureteral occlusion reduced renin release to 10 ± 3 μg AI min^-1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2 μg min^-1kg^-1body wt) to stimulate β-adrenoceptor activity increased renin release from 13 ± 4 μg AI min^-1to 68 ± 8 μg AI min^-1during ureteral occlusion. Intrarenal endothelin infusion (1 ng min^-1kg^-1body wt) reduced renin release to 22 ± 3 μg AI min^-1during continuous isoproterenol infusion and ureteral occlusion. Hence endothelin inhibits renin release induced by renal arterial constriction or ureteral occlusion. Similar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulating β-adrenergic activity suggest a direct effect of endothelin on the juxtaglomerular cells.     

Plasma potassium concentration as a determinant of proximal tubular NaCl and NaHCO3 reabsorption in dog kidneys

To examine whether an acute increase in plasma potassium concentration ([K]_p) may inhibit proximal tubular transport, clearance studies were performed in seven anaesthetized, volume expanded dogs treated with amiloride (1 mg kg^-1body wt) to block tubular potassium secretion, and with bumetanide (30 μg kg^-1body wt) to inhibit NaCl reabsorption in Henle's loop. As [K]_p was raised in steps from 2.6 ± 0.2 to 7.9 ± 0.2 mm , bicarbonate, chloride, and sodium reabsorption decreased by 232 ± 56, 520 ± 59 and 958 ± 112 μmol min^-1, respectively, at constant glomerular filtration rate (GFR). On average, the molar ratio between the inhibitory effects on bicarbonate and chloride reabsorption were 1:2.2–2.4. Reabsorption was calculated at GFR 100 ml min^-1: (reabsorption 100/GFR (mmol min^-1). It was inversely correlated to In [K]_p with r=–0.82 for bicarbonate and with r =–0.89 for chloride. Fractional potassium reabsorption remained constant at 0.31 ± 0.03. Administration of acetazolamide (100 mg kg^-1body wt) in eight dogs at [K]_p 8 mm reduced fractional reabsorption of bicarbonate, chloride and sodium as much as in previous studies on normokalaemic dogs. We conclude that acute elevation of [K]_p inhibits NaHCO₃ transport and passive proximal tubular NaCl reabsorption. This inhibition is not related to changes in potassium secretion and carbonic anhydrase activity, but may be secondary to depolarization of the basolateral membrane.     

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E₂ (PGE₂). In the first group, intravenous infusion of ANF (50 ng min^-1kg^-1body wt) reduced basal PGE₂ release from 4.4 ± 0.8 pmol min^-1to 1.8 ± 0.7 pmol min^-1. In the second group, intrarenal infusion of an α-adrenoceptor agonist, phenylephrine (2.5–6.75 μg min^-1), raised PGE₂ release from 2.7 ± 0.5 pmol min^-1to 7.5 ± 1.3 pmol min^-1. During continuous α₁-adrenergic stimulation, intravenous infusion of ANF (100 ng min^-1kg^-1body wt) reduced PGE₂ release to 3.5 ± 1.0 pmol min^-1. These results demonstrate that ANF reduces basal and α₁-adrenergic stimulated renal PGE₂ release.     

Regulation of porcine biliary secretion by secretin

The importance of physiological plasma levels of secretin in biliary bicarbonate secretion is not known. However, in anaesthetized pigs the substantial hepatic output of bicarbonate into the duodenum in response to low doses of secretin exceeds pancreatic bicarbonate output. The aim was therefore to study the relationship between duodenal acidification, secretin and hepatic biliary bicarbonate output in the conscious pig. Göttingen minipigs (n = 22) were cholecystectomized and the common bile duct catheterized. The biliary bicarbonate secretion in response to intraduodenal HCl, secretin or pentagastrin given intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and pentagastrin given intravenously augmented hepatic bicarbonate output and plasma secretin concentrations significantly. The secretin response to acidification was sufficient to explain the subsequent increase in biliary bicarbonate secretion. Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma increased postprandially. Exclusion of bile salts from the duodenum abolished postprandial increase in bile volume and increased release of CCK in fasting and fed pigs whereas secretin release was diminished. The results demonstrate that hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore may have a physiological role in duodenal neutralization.     

The effect of glucagon,dibutyrylic cyclic AMP and insulin on bile production in the intact rat and the perfused rat liver

The effect of glucagon, dibutyrylic cyclic AMP (DBcAMP) and insulin on bile flow and composition was studied in fasting, Nembutal anesthetized intact rats and perfused rat livers. In intact rats the infusion of glucagon (0.5 μg · kg b. w^-1· min^-1) resulted in a parallel increase in bile flow and ¹⁴C-erythritol clearance of approx. 20%. The biliary excretion rate of electrolytes increased, whereas the net ductular fluid transport and the excretion rate of bile acids remained unchanged. Thus glucagon choleresis in intact rats appears to be due to a stimulation of the bile acid independent fraction of canalicular bile production. A similar effect was seen when DBcAMP (0.5 μmol · kg b. w.^-1· min^-1) and insulin (1 U · kg b. w.^-1) was given. In the perfused liver glucagon or DBcAMP also increased bile flow. However, bile acid excretion rate also increased and the rise in bile flow was proportional to the rate of taurocholate administration. This effect may be due to uneven distribution of perfusate flow. Insulin was totally without effect on bile production in the perfusion experiments. It is concluded that the choleretic effect of glucagon and insulin is dependent on unknown factors which may be related to extrahepatic actions of the hormones.