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.     

Effect of hypertonic saline infusion on renal vascular resistance in anesthetized dogs.

Changes in renal vascular resistance (RVR) and their mechanisms were investigated following infusion of 7.5% hypertonic saline (4 ml/kg) in anesthetized dogs. In all animals the left kidney was perfused at a constant perfusion flow (59 +/- 6 ml/min) with heparinized blood using a pulsatile roller pump. Renal perfusion pressure (RPP), systemic blood pressure (SBP), central venous pressure (CVP), and heart rate (HR) were measured simultaneously. Electrical stimulation of renal sympathetic nerves was also performed to evaluate the neurally mediated change in renal vasculature before and after infusion of hypertonic saline. In animals with intact vagi, intravenous administration of hypertonic saline resulted in significant increases in both mean blood pressure (MBP) and CVP, and caused significant decreases in HR and RVR. These effects were not affected by bilateral cervical vagotomy. In both intact and vagotomized animals, changes in RVR in response to renal nerve stimulation were attenuated after infusion of hypertonic saline. These results suggest that reduction in RVR after intravenous infusion of hypertonic saline is not a reflex effect mediated by vagal afferents. Instead, vascular response of the renal artery to hypertonic saline may result from a suppression of neurotransmission from renal sympathetic nerve endings to renal vascular smooth muscle.     

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 x min-1 x 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 x min-1 x 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 0lood 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 x min-1 x kg b.w.-1 or higher before any general vascular reactions lere recorded, indicating that the liver has a high capacity for inactivating SP.     

Effect of intranasal substance P on the Parkinsonian syndrome

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Odessa Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 16–19, January, 1992.     

Effect of substance P on an experimental parkinsonian syndrome

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 10, pp. 404–407, October, 1989.     

Influence of central respiratory activity on the cough response in anesthetized dogs.

Cough responses evoked by mechanical stimulation of the tracheobronchial mucosa in anesthetized and tracheostomized dogs were studied. The most common response was a group of coughs. Phase relationships between coughing and spontaneous respiration during the cough initiation and resolution periods were categorized as either synchronized or unsynchronized. We defined the synchronization as the coincidence of an expiratory thrust and the early-expiratory phase of respiration. During the cough initiation period, the incidence of synchronization increased as central respiratory activity was enhanced by hypercapnia or as the cough center's activity was suppressed by deep anesthesia. Synchronization decreased as central expiratory activity was enhanced by expiratory threshold loading. During the cough resolution period, synchronization occurred in conjunction with a gradual decrease in the cough center's activity. Coughing could be evoked when the dog was made apneic either by hyperventilation or by the Hering-Breuer reflex. In either case, apnea persisted after coughing subsided. These findings suggest that mechanical stimulation directly activates the cough center rather than the respiratory center; and that synchronization is determined by the relative strengths of the respiratory and cough center's activities.     

Hemodynamic responses during acute normovolemic hemodilution in anesthetized dogs.

Acute normovolemic hemodilution was induced by progressive replacement of blood by dextran (molecular weight 150,000) in anesthetized artificially ventilated dogs. Experiments were performed on dogs with intact autonomic innervation, dogs with beta-adrenergic blockade, dogs with cholinergic blockade, dogs with bilateral vagotomy, and dogs with combined bilateral vagotomy plus beta-adrenergic blockade. Hemodilution induced an increase in cardiac-output in all the groups. However, in dogs with low control heart rate (dogs with intact autonomic innervation, and dogs with beta-adrenergic blockade), cardiac-output increase was almost wholly due to an increase in heart rate. Whereas, in dogs with high control heart rate (dogs with cholinergic blockade, dogs with bilateral vagotomy, and dogs with combined bilateral vagotomy plus beta-adrenergic blockade), the increase in cardiac-output was almost wholly due to an increase in the stroke-volume. The increase in heart rate in dogs with intact autonomic innervation was not significantly different from the heart rate increase in dogs with beta-adrenergic blockade. In dogs with low control heart rate (beta-receptor blockade), hemodilution induced tachycardia, which was not significantly different from the response induced in intact dogs. This shows that the cardioacceleration was primarily mediated through the efferent vagus nerves, and the efferent sympathetic nerves did not make significant contribution in the reflex.     

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.     

Effect of substance P on neuronal activity in the antinociceptive system

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 12, pp. 651–654, December, 1989.