sincalide and Hyperemia

We have studied the potential role of CCK as a regulator/modulator of the postprandial increase in gastrointestinal blood flow. Rainbow trout (Oncorhynchus mykiss) were instrumented with pulsed Doppler flow probes to measure the effects of CCK on cardiac output and gastrointestinal blood flow. Furthermore, vascular preparations were used to study the direct effects of CCK on the vessels. In addition, we used in situ perfused hearts to further study the effects of CCK on the cardiovascular system. When the sulfated form of CCK-8 was injected at a physiological concentration (0.19 pmol/kg) in vivo, there was a significant increase in the gastrointestinal blood flow (18 +/- 4%). This increase in gastrointestinal blood flow was followed by a subsequent increase in cardiac output (30 +/- 6%). When the dose was increased to 0.76 pmol/kg, there was only a 14 +/- 6% increase in gastrointestinal blood flow; possibly due to a dose-dependent increase in the gill vascular resistance as previously reported or a direct effect on the heart. Nevertheless, CCK did not affect the isolated vessel preparations, and thus, it seems unlikely that CCK has a direct effect on the blood vessels of the second or third order. CCK did, however, have profound effects on the dynamics of the heart, and without a change in cardiac output, there was a significant increase in the amplitude (59 +/- 4%) and rate (dQ/dt: 55 +/- 4%; -dQ/dt: 208 +/- 49%) of the phasic flow profile. If and how this might be coupled to a postprandial gastrointestinal hyperemia remains to be determined. We conclude that CCK has the potential as a regulator of the postprandial gastrointestinal blood flow in fish and most likely has its effect by inducing a gastrointestinal hyperemia. The mechanism by which CCK acts is at present unknown.

Topics: Amino Acid Sequence; Animals; Cardiac Output; Conserved Sequence; Diastole; Gastrointestinal Agents; Gastrointestinal Tract; Hyperemia; Oncorhynchus mykiss; Postprandial Period; Regional Blood Flow; Sincalide; Systole

This study was performed to identify the possible neural mechanisms and mediators that underlie the gastric mucosal hyperemia evoked by cholecystokinin octapeptide (CCK-8). Gastric mucosal blood flow in anesthetized rats was assessed by the clearance of hydrogen and gastric acid secretion determined in the luminally perfused stomach. The gastric mucosal hyperemic effect of a low dose of CCK-8 (0.04 nmol/min iv infusion for 7 min) was abolished by inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (15 mg/kg iv) and significantly blunted by defunctionalization of afferent neurons with a neurotoxic dose of capsaicin (125 mg/kg sc). The hyperemic reaction to a high dose of CCK-8 (0.2 nmol/min) was not significantly affected by these pharmacological maneuvers. The vasodilator response to low-dose CCK-8 (0.04 nmol/min) was further analyzed and found to be inhibited by acute bilateral subdiaphragmatic vagotomy, atropine (1 mumol/kg ip), and the antagonistic calcitonin gene-related peptide (CGRP) fragment CGRP-(8-37) (6 nmol/ min ia). Cyclooxygenase inhibition with indomethacin (10 mg/kg ip) was ineffective. The CCK-8-induced increment of gastric acid secretion was not significantly altered by any of these procedures. These results indicate that the gastric vasodilator effect of submaximal doses of CCK-8 is brought about by a vagovagal reflex that involves acetylcholine, CGRP or a related peptide, and nitric oxide as vasodilator messengers.

Topics: Animals; Calcitonin Gene-Related Peptide; Capsaicin; Female; Gastric Acid; Gastric Mucosa; Hyperemia; Nervous System Physiological Phenomena; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptide Fragments; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sincalide; Vagotomy

The purpose of the present study is to assess the role of capsaicin-sensitive afferent nerves of the gut in bile-oleate-induced intestinal hyperemia. In anesthetized rats, intestinal blood flow (BF) was determined with a pulsed Doppler flowmeter. Systemic arterial blood pressure and heart rate were also measured. Test solutions containing either 40 or 80 mM oleic acid, combined with 10% natural bile, were introduced into the jejunum and produced abrupt increases in BF (64 +/- 12 and 118 +/- 14% of control, respectively). The vasodilator response was abolished by pretreatment with systemic capsaicin in neonatal life and by topical application of either capsaicin or lidocaine to the mucosa in adult animals. The response was inhibited 69 +/- 6% by an antiserum to vasoactive intestinal peptide. We found no significant inhibition of the vasodilator response by pretreating animals with antisera to cholecystokinin octapeptide or substance P, nor with hexamethonium, atropine, or reserpine. It appears that bile-oleate-induced intestinal vasodilation involves primary afferent nerve fibers of gut that release vasoactive intestinal peptide.

Topics: Animals; Atropine; Bile; Blood Pressure; Capsaicin; Female; Heart Rate; Hexamethonium; Hexamethonium Compounds; Hyperemia; Immune Sera; Jejunum; Male; Mesenteric Arteries; Oleic Acid; Oleic Acids; Rats; Rats, Inbred Strains; Reference Values; Regional Blood Flow; Reserpine; Sincalide; Splanchnic Circulation; Substance P; Vasoactive Intestinal Peptide

The purpose of this study was to evaluate the roles of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), and glucagon in the local regulation of the lipid-induced intestinal hyperemia. Total blood flow and the arteriovenous hormone concentration gradient were measured in isolated jejunal loops of anesthetized dogs with either saline, bile (10% in normal saline), oleic acid (40 mM in normal saline), or oleic acid and bile in the lumen. The bile-oleic acid mixture increased both blood flow (+21 +/- 7%) and VIP release (+118 +/- 7%), while CCK release was considerably less. There was a transient rise in glucagonlike immunoreactivity but no change in pancreatic glucagon release. Neither bile nor oleic acid alone altered either local blood flow or hormone release. Infusion of VIP into the arterial circulation of the jejunum significantly reduced vascular resistance (-11 +/- 4%) but at a dose (150 ng . min-1 X 100 g-1) 10 times that released in response to the bile-oleic acid mixture. This study indicates that oleic acid increases both blood flow and intestinal hormone production only when present in the lumen in micellar form and suggests that VIP could play a role in the jejunal vascular response to fat.

Topics: Animals; Bile; Blood Pressure; Cholecystokinin; Dogs; Drug Combinations; Female; Gastrointestinal Motility; Glucagon; Hyperemia; Injections, Intra-Arterial; Jejunum; Male; Oleic Acid; Oleic Acids; Regional Blood Flow; Sincalide; Vascular Resistance; Vasoactive Intestinal Peptide