Effect of phenoxybenzamine on mesenteric blood flow in irradiated rats

Reactivity of the superior mesenteric artery has been studied in rat Wistar by infusion of biogenic amines (noradrénaline, dopamine, serotonin, acetylcholine and histamine) in presence of phenoxybenzamine. A decrease in reactivity of the post-synaptic alpha receptor located on the mesenteric vascular smooth muscle cell was seen three days after irradiation by 2 Kr.     

Effect of mesenteric vascular congestion on reflex control of renal blood flow

Portal hypertension initiates a splenorenal reflex, whereby increases in splenic afferent nerve activity and renal sympathetic nerve activity cause a decrease in renal blood flow (RBF). We postulated that mesenteric vascular congestion similarly compromises renal function through an intestinal-renal reflex. The portal vein was partially occluded in anesthetized rats, either rostral or caudal to the junction with the splenic vein. Portal venous pressure increased (6.5 +/- 0.1 to 13.2 +/- 0.1 mmHg; n = 78) and mesenteric venous outflow was equally obstructed in both cases. However, only rostral occlusion increased splenic venous pressure. Rostral occlusion caused a fall in RBF (-1.2 +/- 0.2 ml/min; n = 9) that was attenuated by renal denervation (-0.5 +/- 0.1 ml/min; n = 6), splenic denervation (-0.2 +/- 0.1 ml/min; n = 11), celiac ganglionectomy (-0.3 +/- 0.1 ml/min; n = 9), and splenectomy (-0.5 +/- 0.1 ml/min; n = 6). Caudal occlusion induced a significantly smaller fall in RBF (-0.5 +/- 0.1 ml/min; n = 9), which was not influenced by renal denervation (-0.2 +/- 0.2 ml/min; n = 6), splenic denervation (-0.1 +/- 0.1 ml/min; n = 7), celiac ganglionectomy (-0.1 +/- 0.3 ml/min; n = 8), or splenectomy (-0.3 +/- 0.1 ml/min; n = 7). Renal arterial conductance fell only in intact animals subjected to rostral occlusion (-0.007 +/- 0.002 ml.min(-1).mmHg(-1)). This was accompanied by increases in splenic afferent nerve activity (15.0 +/- 3.5 to 32.6 +/- 6.2 spikes/s; n = 7) and renal efferent nerve activity (32.7 +/- 5.2 to 39.3 +/- 6.0 spikes/s; n = 10). In animals subjected to caudal occlusion, there were no such changes in renal arterial conductance or splenic afferent/renal sympathetic nerve activity. We conclude that the portal hypertension-induced fall in RBF is initiated by increased splenic, but not mesenteric, venous pressure, i.e., we did not find evidence for intestinal-renal reflex control of the kidneys.     

Vascular perfusion limits mesenteric lymph flow during anaphylactic hypotension in rats

To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.     

Adenosine mediation of mesenteric blood flow.

The mesenteric circulation is regulated by multiple mechanisms, there is sufficient reason to support the suspicion that local metabolic factors are especially important in the control of intestinal vasculature. Of these, adenosine, a purine nucleoside and mesenteric vasodilator, may be the messenger of the intestinal tissue to signal appropriate responses of the intestinal vessels. The evidence supporting the candidacy of the nucleoside as a local regular of mesenteric circulation may be summarized, as follows: Adenoside is present in the tissue of the gut in measurable quantities. Exogenous adenosine is a powerful dilator of mesenteric resistance vessels. Blockade of adenosine receptors in the mesenteric circulation interferes significantly with three autoregulatory phenomena, i.e., postprandial hyperemia, pressure-flow autoregulation, and reactive hyperemia. The evidence which weakens the role of adenosine as mesenteric vasoregulator includes: Findings in several reports that adenosine depressed intestinal oxygen consumption. The failure of adenosine receptors to inhibit some autoregulatory hyperemias of the gut and the rather limited amount of evidence regarding tissue adenosine release in autoregulatory responses of the gut's vasculature.     

Effect of isoproterenol or exercise on pulmonary lymph flow and hemodynamics

Experiments were performed to determine whether different methods of increasing cardiac output would have similar effects on lung lymph flow, and to assess the contribution of the microvasculature (fluid-exchanging vessels) to the total calculated pulmonary vascular resistance. Yearling unanesthetized sheep with chronic vascular catheters and lung lymph fistulas underwent intravenous infusions of isoproterenol at 0.2 micrograms X kg-1. min-1 (n = 8) or were exercised on a treadmill (n = 16). Both isoproterenol and exercise increased cardiac output, lowered calculated total pulmonary and systemic vascular resistances, and had no effect on the calculated pulmonary microvascular pressure. Isoproterenol infusions did not affect lung lymph flow, whereas exercise increased lung lymph flow in proportion to the increase in cardiac output. We conclude that 1) the sheep has a different pulmonary hemodynamic response to exercise than dogs and man, 2) the microvasculature is recruited during exercise-induced but not isoproterenol-induced increases in cardiac output, and 3) the microvasculature represents only a small proportion of the total calculated pulmonary vascular resistance.     

Opioid receptors in rat cardiac sarcolemma: effect of phenylephrine and isoproterenol

The present study demonstrates the presence of opioid receptors in the rat cardiac sarcolemma isolated by the hypotonic LiBr-shock procedure. Opioid binding was measured by using [3H]U69 593, [3H](2-D-penicillamine,5-D-penicillamine)enkephalin ([3H]DPDPE) or [3H][D-Ala2,MePhe4,Gly-(ol)5]enkephalin ([3H]DAGO) as selective radioligands for K, delta and mu opioid receptors, respectively. Both the K- and delta-selective ligands exhibited highly specific (75-86%) binding, saturable at a concentration of about 20 nM. No specific binding for the selective agonist DAGO was observed. A marked increase in both [3H]U69 593 and [3H]DPDPE binding was observed after incubation of the sarcolemma with the alpha-adrenoceptor agonist phenylephrine or with the beta-adrenoceptor agonist isoproterenol. These stimulatory effects were associated with an increase in the Bmax values, a decrease in the Kd values, and were completely antagonized by the respective antagonists phentolamine and propranolol.     

Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans.

The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure (BPa) decreased by 23%-30% and heart rate (fc) increased but only during NTG infusion (+22%; P less than 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: -26%, P less than 0.01; SNP: -34%, P less than 0.02] and subcutaneous vascular resistance changed only with SNP (-31%, P less than 0.02). After hypotension was discontinued the subcutaneous blood flow decreased (-13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between fc and BPa (NTG: r = -0.525, P less than 0.01; SNP: r = -0.622, P less than 0.01) as well as with subcutaneous blood flow (NTG: r = -0.653, P less than 0.001; SNP: r = -0.573, P less than 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W.m-1.degree C-1 vs SNP 0.42 (SEM 0.1) W.m-1.degrees C-1, P less than 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P less than 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects.     

The effect of taurine on mesenteric blood flow and organ injury in sepsis

Endotoxin decreases mesenteric blood flow and inflicts organ injury via free radicals. We investigated whether taurine, an endogenous antioxidant and vasodilator, could attenuate the deleterious effects of endotoxin in a mouse model of sepsis. Swiss albino mice were allocated into four groups and treated either with taurine (150 mg/kg, i.p. at 0(th), 8(th), 16(th) h) or its solvent sterile saline (NaCl 0.9%, w/v) while E. coli endotoxin (20 mg/kg, i.p.) or its solvent saline were also given at 8(th) h. At 24(th) h the animals were anaesthetized and the mesenteric blood flow was measured by using perivascular ultrasonic Doppler-flowmeter. The animals were then exsanguinated, the spleen, liver, and kidneys were isolated for histopathological examination. Thiobarbituric acid-reacting substances (TBARS), glutathione, and myeloperoxidase activity were determined in the liver samples. Endotoxin significantly decreased the mesenteric blood flow and glutathione levels in liver while TBARS and myeloperoxidase activity were increased. However, taurine did not block the deleterious effects of endotoxin nor it did attenuate the histopathological injury. Therefore, we concluded that endotoxin-induced organ injury via free radicals is resistant to blockade by taurine.     

Effect of experimental diabetes on isolated rat heart responsiveness to isoproterenol

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the sensitivity and responsiveness of the myocardium to the effects of isoproterenol. Experimental diabetes was induced by intravenous administration of either 65 mg/kg alloxan or 60 mg/kg streptozotocin. The positive inotropic and cardiac relaxant effects of isoproterenol were studied at various time points after the induction of diabetes. There were no changes either in the sensitivity or in the maximum responses of diabetic rat hearts to the positive inotropic effect of isoproterenol at any time point studied. However, the cardiac relaxant effect of isoproterenol was depressed in acute as well as chronic diabetic rat hearts when compared with age-matched controls. Ventricular noradrenaline content was unchanged in 180-day diabetic rat hearts indicating the absence of a diabetes-induced sympathetic neuropathy in the heart. The depressed relaxing effect of isoproterenol may have resulted from alterations in energy utilization and sarcoplasmic reticular function in diabetic rat hearts.     

Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease

The mesenteric and intestinal blood flow is organized and regulated to support normal intestinal function, and the regulation of blood flow is, in part, determined by intestinal function itself. In the process of the development and adaptation of the intestinal mucosa for the support of the digestive processes and host defense mechanisms, and the muscle layers for propulsion of foodstuffs, a specialized microvascular architecture has evolved in each tissue layer. Compromised mesenteric and intestinal blood flow, which can be common in the elderly, may lead to devastating clinical consequences. This problem, which can be caused by vasospasm at the microvascular level, can cause intestinal ischaemia to any of the layers of the intestinal wall, and can initiate pathological events which promote significant clinical consequences such as diarrhea, abdominal angina and intestinal infarction. The objective of this review is to provide the reader with some general concepts of the mechanisms by which neurohumoral vasoactive substances influence mesenteric and intestinal arterial blood flow in health and disease with focus on transmural transport processes (absorption and secretion). The complex regulatory mechanisms of extrinsic (sympathetic-parasympathetic and endocrine) and intrinsic (enteric nervous system and humoral endocrine) components are presented. More extensive reviews of platelet function, atherosclerosis, hypertension, diabetes mellitus, the carcinoid syndrome, 5-hydroxytryptamine and nitric oxide regulation of vascular tone are presented in this context. The possible options of pharmacological intervention (e.g. vasodilator agonists and vasoconstrictor antagonists) used for the treatment of abnormal mesenteric and intestinal vascular states are also discussed.     

Effects of sodium nitroprusside-induced hypotension on the cerebral and hindlimb blood flow in dogs

Sodium nitroprusside (SNP) has been commonly used as a vasodilator agent for deliberate hypotension with general anesthesia. The purpose of this study was to observe whether cerebral blood flow (CBF) was significantly reduced when SNP infusion was accomplished to decrease peripheral blood flows with systemic hypotension. We conducted the experiments in 15 pentobarbital-anesthetized dogs. CBF was measured in 7 dogs using a venous outflow method. Hindlimb blood flow (HBF) serving as a representative of the peripheral circulations was obtained by flow measurement in the femoral artery in 8 dogs. The systemic arteral pressure (SAP) was decreased stepwise (approximately 5 mmHg for each step) by adjusting the SNP infusion rate. During the systemic hypotension, the CBF remained fairly constant despite a marked decline in the mean SAP to 40 mmHg. The calculated cerebral vascular resistance was progressively decreased with the systemic hypotension. On the contrary, a reduction in the HBF was observed accompanying the fall in SAP. When the mean SAP was decreased to 50 mmHg, the HBF was only 46.3 +/- 7.6% of the control value. The calculated hindlimb vascular resistance was slightly elevated during the whole course of SNP-induced hypotension. The results reveal the disparity between the brain and hindlimb in the resistance and flow responses to SNP-induced hypotension. The constancy of CBF subserves adequate brain perfusion when deliberate hypotension is conducted for surgery in the peripheral organs.     

A model of blood flow in the mesenteric arterial system

Background  

There are some early clinical indicators of cardiac ischemia, most notably a change in a person's electrocardiogram. Less well understood, but potentially just as dangerous, is ischemia that develops in the gastrointestinal system. Such ischemia is difficult to diagnose without angiography (an invasive and time-consuming procedure) mainly due to the highly unspecific nature of the disease.