pituitrin and Hyperemia

Gastric mucosal perfusion is increased in portal-hypertensive gastropathy, and this may contribute to gastric bleeding from these lesions. Therefore drugs reducing gastric mucosal perfusion may be beneficial in the treatment of overt bleeding from portal-hypertensive gastropathy. In this study gastric mucosal perfusion was assessed in 28 cirrhotic patients with portal-hypertensive gastropathy under basal conditions and after double-blind intravenous administration of vasopressin (0.4 U/min), glypressin (2-mg injection) or placebo, with laser-Doppler flowmetry and reflectance spectrophotometry. Vasopressin and glypressin induced a significant increase in blood pressure and a decrease in heart rate. These effects were more pronounced in the vasopressin group. Both vasopressin and glypressin induced a sustained and similar reduction in gastric mucosal perfusion as assessed by laser-Doppler flowmetry (-36% +/- 8% and -34% +/- 6%, respectively; p < 0.05 with respect to basal values and with respect to the control group), whereas placebo had no effect. Both drugs significantly reduced the oxygen content of the gastric mucosa; however, the impairment in mucosal oxygenation was greater (p < 0.05) in the vasopressin group (-17% +/- 3%) than in the glypressin group (-6% +/- 0.1%). We conclude that the increased gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy may be reduced by either vasopressin or glypressin. These findings support the use of these drugs in clinical trials treating bleeding portal-hypertensive gastropathy. The lower reduction in gastric mucosal oxygen content observed with glypressin could decrease the incidence of ischemic adverse events associated with the use of vasopressin.

Topics: Double-Blind Method; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Hyperemia; Hypertension, Portal; Laser-Doppler Flowmetry; Liver Cirrhosis; Lypressin; Male; Middle Aged; Oxygen; Regional Blood Flow; Spectrophotometry; Stomach Diseases; Terlipressin; Vasopressins

Portal hypertension is associated with splanchnic vasodilation which is claimed responsible for the maintenance of chronically elevated portal pressure. Vasopressin analogues are used in the treatment of acute variceal bleeding, since they effectively reduce splanchnic blood flow and portal pressure. Dehydration stimulates the release of endogenous vasopressin release. Here we compared the effects of deprivation of drinking water for 18 h with those of vasopressin infusion on mesenteric hemodynamics in portal vein-ligated (PVL) and sham-operated (SHAM) rats. Blood flow in the superior mesenteric artery was measured with the ultrasonic transit time shift technique. Deprivation of drinking water had no hemodynamic effects in SHAM rats, but completely reversed the mesenteric hyperemia and portal hypertension in PVL rats to figures measured in SHAM rats, without altering blood pressure. Similarly, intravenous infusion of low doses of arginine vasopressin (1-10 pmol/min) selectively reduced mesenteric blood flow in PVL rats but had little effect in SHAM rats. These data suggest that control of water balance or aquaretic drugs might have beneficial effects on splanchnic hemodynamics and portal pressure in advanced liver disease, possibly by stimulating endogenous vasopressin release.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Disease Models, Animal; Hyperemia; Hypertension, Portal; Ligation; Liver Diseases; Male; Mesenteric Artery, Superior; Portal Vein; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilation; Vasopressins; Water Deprivation

We recently reported that vasopressin analogues correct the in vitro vascular hyporeactivity to adrenergic vasoconstrictors in portal hypertensive rats. The aim of the present study was to determine whether vasopressin reduces splanchnic blood flow in portal vein-ligated (PVL) rats by restoring vasoconstrictor responsiveness in vivo. The ultrasonic transit time-shift technique was used for blood flow measurements. At basal conditions, blood flow through the superior mesenteric artery was elevated 1.6-fold in PVL rats as compared with sham-operated (SHAM) control rats. PVL rats also exhibited blunted mesenteric constrictor responses to the adrenoceptor agonist, phenylephrine (0.03-1 micromol x min(-1) x kg(-1)). Terlipressin (2-20 microg x k(-1)) and arginine vasopressin (3-300 pmol x min(-1) x kg(-1)) dose-dependently reduced, and at the highest doses, even abolished, the difference in mesenteric blood flow (MBF) between PVL and SHAM rats. When expressed as percent changes relative to baseline, mesenteric arterial responses to terlipressin and arginine vasopressin were found to be enhanced in PVL rats as compared with SHAM rats. Moreover, pretreatment with terlipressin (20 microg x kg(-1)) reversed the mesenteric hyporesponsiveness to phenylephrine of PVL rats. These vasopressin effects were independent of the nitric oxide (NO) pathway, because they were not mimicked by inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) (0.1-10 mg x kg(-1)). These data indicate that pharmacological doses of vasopressin reverse the splanchnic hyperemia by restoring the responsiveness to adrenergic vasoconstrictors in portal hypertensive rats.

Topics: Anesthesia; Animals; Hemodynamics; Hyperemia; Hypertension, Portal; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; Splanchnic Circulation; Vasoconstriction; Vasopressins

We compared changes in gastric mucosal blood flow (GMBF) and left gastric artery blood flow (LGABF) in response to pharmacological, physiological, and pathological stimuli. GMBF and LGABF were measured by the hydrogen gas clearance and perivascular ultrasonic transit time techniques, respectively, under baseline conditions and following intravenous infusion of vasopressin or pentagastrin, isovolemic hemodilution, or gastric perfusion with HCl-taurocholate. Blood flow changes following vasopressin or hemodilution were significantly larger in the left gastric artery than in the gastric mucosa. In contrast, the increment in blood flow associated with pentagastrin-stimulated acid secretion was significantly greater in the gastric mucosa than in the extramural artery. Barrier disruption with acid-taurocholate induced similar changes in both measurement sites. The gastric hyperemia induced by either mechanism was significantly attenuated by blockade of NO synthesis. These data demonstrate that although functional changes in GMBF are primarily supported by changes in blood flow at the extramural gastric arteries, the gastric mucosal microvasculature is also under the influence of independent local control mechanisms.

Topics: Anemia; Animals; Arteries; Female; Gastric Acid; Gastric Mucosa; Hemodilution; Hydrogen; Hyperemia; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pentagastrin; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Stomach; Taurocholic Acid; Ultrasonography; Vasoconstrictor Agents; Vasopressins

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.

Topics: Animals; Arterial Occlusive Diseases; Arteries; Coronary Circulation; Dogs; Female; Hemodynamics; Homeostasis; Hyperemia; Male; Myocardial Contraction; Vasopressins

The effect of 0.15 IU/min vasopressin (VA) administered intracoronarily on postocclusion reactions following 15 sec, 30 sec, 60 sec, and 120 sec occlusions of the left coronaries of the isolated fibrillating dog heart were studied at constant pressure or constant volume perfusion with arterial blood of another dog. Basal perfusion pressure was kept at the level of 150 mmHg. Preocclusion state and postocclusion reactions were characterized by changes in coronary conductance. Peak conductance, maximum conductance, reactivity, time to peak conductance, mean transit time and repayment were computed for characterizing reactive hyperaemia. In the control state the post-occlusive conductance--time curve was higher, but shorter in duration with constant pressure perfusion than with constant volume perfusion. Upon the administration of VA, basal conductance decreased considerably while with constant pressure perfusion the hyperaemic reactions underwent hardly any change. In contrast, using constant volume perfusion, the duration of reactive hyperaemia was shortened by VA. Consequently, the differences in mean transit time observed in the controls resulted from the unequal perfusion techniques disappeared on the application of VA. On both constant pressure and constant volume perfusion, maximum conductance decreased as a result of the decrease in basal conductance, therefore the reactivity of the coronary vessels increased markedly. It is concluded that myogenic vasorelaxation may contribute to reactive hyperaemic responses not only on brief, but also on prolonged occlusion. The basal vascular tone is of importance in the coronary adaptation to ischaemia.

Topics: Animals; Blood Circulation; Coronary Disease; Dogs; Heart; Hyperemia; Myocardium; Perfusion; Vasopressins

Topics: Epinephrine; Hemostasis, Surgical; Humans; Hyperemia; Ornithine; Surgery, Oral; Vasopressins

In the chloralosed cat reactive hyperaemia to vessel occlusion, and vascular escape associated with vasoconstriction produced by drugs, have been examined in the hindquarters and splanchnic region, and following periaterial mesenteric nerve stimulation in the splanchnic region. The hyperaemic responses were not of a purinergic nature or mediated by an acetylcholine, histamine, dopamine or beta-adrenoceptor stimulant-like substance, and were independent of adrenergic innervation. These responses may respresent a local mechanism by which the vasculature produces vasodilation in response to reduced blood flow.

Topics: Anesthesia; Angiotensin II; Animals; Arteries; Blood Pressure; Cats; Female; Heart Rate; Hindlimb; Hyperemia; Male; Regional Blood Flow; Reserpine; Sympathetic Nervous System; Vasoconstrictor Agents; Vasopressins

The local intracoronary application of the alpha adrenergic blocking agents phenoxybenzamine or dibenamine, in open chest anesthetized dogs, regularly resulted in maximal coronary vasodilatation thus abolishing reactive hyperemia. Infusion of vasopression or angiotensin returned coronary flow to near control levels and restored reactive hyperemia. It is thus concluded that although alpha blocking agents can relax coronary vessel smooth muscle, reactive hyperemia does not appear to be mediated through the inhibition of alpha adrenergic constrictor tone.

Topics: Adrenergic alpha-Antagonists; Angiotensin II; Animals; Coronary Vessels; Dibenzylchlorethamine; Dogs; Heart; Hyperemia; Phenoxybenzamine; Vasopressins

The infiltration of a vasoconstrictor causes bleeding to diminish in the surgical field. Adrenalin is such a vasoconstrictor, but because of its metabolic action, acidosis develops in the tissue followed by decreased oxygen tension, a reactive hyperemia. This can of course cause postoperative hemorrage and edema.

Topics: Acidosis; Body Temperature; Epinephrine; Hemostasis; Humans; Hyperemia; Jaw; Oral Hemorrhage; Ornithine; Oxygen; Surgery, Oral; Thermography; Vasopressins

Topics: Animals; Female; Hemorrhage; Hyperemia; Kidney; Male; Rats; Vasopressins

Topics: Acetylcholine; Adaptation, Physiological; Animals; Birds; Blood Circulation; Coronary Vessels; Dibenzylchlorethamine; Epinephrine; Hexamethonium Compounds; Hyperemia; Hypoxia; Isoproterenol; Norepinephrine; Oxytocin; Vasopressins