The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.     

Adrenomedullary origin of the hindquarter vasodilation during the transposition response of the rat

Transposing a rat from the home cage to a new cage produces a cardiovascular response (transposition response) characterized by an increase in hindquarter blood flow with unchanged systemic arterial pressure. Arterial blood samples were collected from rats before and during this response for radioenzymatic assay of catecholamines. During the transposition response, the concentration of adrenaline and noradrenaline in plasma increased about six- and two-fold, respectively. Ablation of the adrenal medulla prevented these changes in plasma catecholamine concentration. Constant i.v. infusion of adrenaline, at rates producing a hindquarter flow approximately matching that observed during the transposition response, evoked an increase in plasma adrenaline concentration also approximately matching the increase observed during the transposition response. It is concluded that the increase in plasma adrenaline secreted from the adrenal medulla is the main cause of the increase in hindquarter blood flow in the transposition response.     

Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3-O-methylglucose. The infused dose of glucose (1 mg. kg body wt(-1). min(-1)) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of D-glucose increased insulin release and islet blood flow; the osmotic control substance 3-O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.     

Vascular reactivity in hypertensive rats after treatment with anti-hypertensive agents

Isolated perfused mesenteric arteries obtained from experimental hypertensive rats (spontaneous and deoxycorticosterone/NaCl) exhibit an increased vascular reactivity to noradrenaline and 5-hydroxytryptamine. The dose response curves obtained exhibited in the threshold dose. After 4 weeks of antihypertensive therapy (a combination of hydrallazine, hydrochlorothiazide and reserpine) which lowered the blood pressures of hypertensive rats to normotensive levels the arteries from the hypertensive animals still exhibited an increased reactivity to vasoconstrictor agents. These results support the hypothesis that the increased reactivity observed in hypertensive animals may be partially due to adaptive structural changes in the blood vessels. However, the persistence of the hyperactivity after antihypertensive therapy seriously questions its involvement in the maintenance of the elevated blood pressure.     

Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41 degrees C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.     

Blood pressure responsiveness to sympathetic agonists in anaesthetised diabetic rats

Chronic diabetes alters sympathetic modulation of the cardiovascular system. In the present work, we examined if the cardiovascular system also demonstrates an impaired responsiveness to sympathetic control. The effects of streptozotocin-induced diabetes on pressure responses to noradrenaline or isoproterenol infusion of diabetic rats in vivo are studied. Systolic and diastolic pressures were recorded through a cannula implanted in the right carotid artery. Increasing doses of noradrenaline or isoproterenol were infused through a catheter implanted in the left jugular vein. The dose-response curves for the effects of noradrenaline on blood pressure were altered in streptozotozin-induced diabetic rats. Noradrenaline induced a statistically significant higher increase of both systolic and diastolic pressure in control than in diabetic rats. The maximum depressor response of systolic pressure to isoproterenol was lower in diabetic than in control animals. Diabetes fully abolishes the effect of beta-adrenoceptor stimulation on diastolic blood pressure. The present results demonstrate that streptozotocin-induced diabetes reduces systolic and diastolic arterial pressure, and diminishes the arterial pressure reactivity to sympathetic stimulation.     

Effect of thyroidectomy on cardiovascular responses to hypoxia and tyramine infusion in fetal sheep

Fetal sheep were thyroidectomized at 80 days' gestation and reoperated at 118-122 days for insertion of vascular catheters. The effects of hypoxaemia and intravenous tyramine infusion on plasma catecholamine concentrations, blood pressure and heart rate were then determined in experiments at 125-135 days' gestation. Age matched intact fetuses were also studied. Thyroidectomy was associated with increased concentrations of noradrenaline, adrenaline and dopamine in some thoracic and abdominal organs, increased noradrenaline concentrations in the cerebellum, and decreased adrenaline concentrations in the hypothalamus, cervical spinal cord, and superior cervical and inferior mesenteric ganglia. Arterial pressure was significantly lower in the thyroidectomized fetuses (34.0 +/- 0.15 mmHg) than in intact fetuses (44.7 +/- 0.2 mmHg; p less than 0.001). In contrast, plasma noradrenaline concentrations were significantly higher in the thyroidectomized fetuses (2.04 +/- 0.25 ng/ml) compared to the intact fetuses (0.99 +/- 0.08 ng/ml; P less than 0.001). In the intact fetuses there was a significant increase in plasma noradrenaline concentration and blood pressure during hypoxaemia, and bradycardia at the onset of hypoxaemia. In contrast, in the thyroidectomized fetuses hypoxaemia did not cause significant change in plasma catecholamine concentrations, blood pressure or heart rate. Infusion of tyramine produced a 1.9-fold increase of plasma noradrenaline in thyroidectomized fetuses compared to a 9.2-fold increase in the intact fetuses (P less than 0.05). Tyramine infusion caused a similar proportional increase of blood pressure in both thyroidectomized and intact fetuses. Heart rate decreased during the tyramine-induced hypertension in the intact fetus, but increased in the thyroidectomized fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of coronary alpha 1-adrenoceptors of the dog heart in dopamine-induced cardiostimulation evidenced by treatment with prazosin

To assess the participation of postjunctional coronary alpha 1-adrenoceptors in the dopamine-induced general circulatory stimulation, pentobarbital-anesthetized open chest dogs were infused with the agent (1-16 micrograms.kg-1.min-1 i.v.) before and after the administration of the alpha 1-selective adrenergic antagonist prazosin (0.15 mg.kg-1). Coronary responses were characterized by the changes of blood flow (electromagnetic flowmeter) and those of calculated vascular conductance. Left ventricular contractile force was measured with a strain gauge arch. In the control state, whereas coronary blood flow increased simultaneously with the dose-dependent hypertensive effect of dopamine, the calculated augmentation of coronary vascular conductance was relatively slight (maximum: greater than or equal to 50%) compared to the very great increase of cardiac inotropism (up to greater than or equal to 250%) and myocardial O2 consumption (up to greater than or equal to 250%). After blocking the alpha 1-adrenoceptors, in spite of the elimination of the hypertensive effect, the inotropic and blood flow actions of dopamine remained unaltered and the calculated value of vascular conductance indicated an enhanced vasodilation (up to 200%). The alpha 2-blocker yohimbine (0.5 mg.kg-1) failed to elicit actions of similar magnitude. It was concluded that postjunctional alpha-adrenoceptor-dependent coronary vasoconstrictor influences compete with metabolically coupled vasodilation during the cardiostimulatory action of dopamine.     

Changes in Sympathetic Nerve Terminals in the Heart of Cold-Exposed Rats

Abstract: Changes in sympathetic nerve terminals of the heart after varying periods of exposure of rats to 4°C were investigated. Two indices were used for changes in the number of noradrenaline storage vesicles, i.e., vesicular dopamine β-hydroxylase (DBH) activity and noradrenaline storage capacity. The latter was obtained after uptake of [³H]noradrenaline; endogenous content, uptake of exogenous noradrenaline, and degree of saturation of the vesicles were calculated using the specific activity of the [³H]noradrenaline. As a measure of tyrosine hydroxylase activity, whole ventricular noradrenaline, dopamine, and dihydroxyphenylacetic acid content were used. After 4 h of cold exposure there was an increase in vesicular endogenous noradrenaline content, uptake, storage capacity, and DBH activity as well as a large increase in whole ventricular dopamine. After 6 h in the cold, vesicular endogenous noradrenaline content, storage capacity, and DBH activity were decreased. The results suggest that during cold exposure there is an initial increase followed by a decrease in the number of functional vesicles in the nerve terminal, which could explain the fluctuations in the rate of noradrenaline release.     

Control of oxygen uptake, microcirculation and glucose release by circulating noradrenaline in perfused rat liver

The effect of noradrenaline on oxygen uptake, on periportal and perivenous oxygen tension at surface acini, on microcirculation and on glucose output were studied in isolated rat livers perfused at constant flow with Krebs-Henseleit-hydrogen carbonate buffer containing 5mM glucose and 2mM lactate. Noradrenaline at 1 microM concentration caused a decrease in oxygen uptake, while at 0.1 microM it led to an increase. Both high and low doses of noradrenaline decreased the tissue surface oxygen tension in periportal and - after a transient rise - in perivenous areas. Noradrenaline at an overall constant flow caused an increase of portal pressure and an alteration of the intrahepatic distribution of the perfusate: at the surface of the liver and in cross sections infused trypan blue led to only a slightly heterogeneous staining after a low dose of noradrenaline but to a clearly heterogeneous staining after a high dose. Both high and low doses of noradrenaline stimulated glucose release. All effects could be inhibited by the alpha-blocking agent phentolamine. In conclusion, control of hepatic oxygen consumption by circulating noradrenaline is a complex result of opposing hemodynamic and metabolic components: the microcirculatory changes inhibit oxygen uptake; they dominate after high catecholamine doses. The metabolic effects include a stimulation of oxygen utilization; they prevail at low catecholamine levels. The noradrenergic control of glucose release is also very complex, involving direct, metabolic and indirect, hemodynamic components.     

Lymphatic transport rate of noradrenaline during adrenergic thermogenesis

The lymphatic concentration of noradrenaline (NA) and lymph flow in the thoracic duct of cold-acclimated rats were measured under conditions of the quasi-stationary thermogenic response to i.v. infused NA. Both parameters increased linearly with increased rate of NA infusion. The lymphatic transport rate of NA is quadratically related to the infusion rate which indicates the same relation for the efflux of NA from blood into the extravascular space. This non-linear efflux of NA causes a non-linear thermogenic response to NA.     

Alpha-adrenergic tone in the coronary circulation of the conscious dog

To examine the role of neural factors in the control of coronary vasoactivity in conscious animals, dogs were supplied with miniature pressure gauges in the aorta and left ventricle (to measure aortic and left ventricular pressures, respectively and with a flow probe on the left circumflex coronary artery (to measure coronary blood flow). The experiments were conducted several weeks after recovery from operation. Stimulation of the carotid chemoreceptor and pulmonary inflation elicited a biphasic reflex response. Initially, coronary vasodilation was observed; coronary blood flow tripled even after changes in metabolic factors were minimized by pretreatment with propranolol. A similar response occurred after a spontaneous deep breath. The coronary vasodilation could be blocked by alpha-adrenergic receptor blockade. The second phase of the response involved an increase in coronary vascular resistance, associated with elevated arterial pressure and an absolute reduction in coronary blood flow and coronary sinus oxygen content. The secondary coronary vasoconstriction was also abolished by alpha-adrenergic blockade. Paradoxically, alpha-adrenergic receptor blockade with phentolamine (at constant heart rate and after beta-adrenergic receptor blockade) did not increase coronary blood flow and reduced coronary vascular resistance only slightly. Selective alpha 1-adrenergic receptor blockade with prazosin and trimazosin on different days induced progressively greater reductions in coronary vascular resistance. Trimazosin was the only alpha-adrenergic receptor blocker to elevate coronary blood flow significantly. It is conceivable, but speculative, that withdrawal of alpha-adrenergic tone may involve activation of an intermediate agent, which is a potent coronary vasodilator. Alternatively, withdrawal of alpha-adrenergic tone may be an important mechanism for immediate control of the coronary circulation, but under more chronic conditions it plays a lesser role as a result of suppression by metabolic factors.     

Comparison of effects of naloxone and catecholamines on acid-base balance in canine hemorrhagic shock

The present study was conducted to compare the effect of naloxone, an opiate receptor antagonist, with catecholamines on acid-base status and survival in dogs subjected to hemorrhagic shock. Arterial lactic acid concentration which had increased during hemorrhage, decreased significantly (P less than 0.05) in naloxone treated animals but increased further in catecholamine treated dogs. Blood bicarbonate concentration and PCO2 which had markedly decreased 1 hr after hemorrhage recovered significantly (P less than 0.05) in naloxone group of animals. On the other hand bicarbonate and pH declined further in noradrenaline group and remained unchanged in dopamine group. These results as well as better survival rate observed in naloxone treated animals suggest the superiority of naloxone over dopamine and noradrenaline, as an adjunct to blood transfusion in the treatment of hemorrhagic shock.     

The effect of chronic alcohol inhalation on blood pressure and the pressor response to noradrenaline and the thromboxane-mimic U46619

Rats were exposed to alcohol vapor for 6 days and the mean blood ethanol concentration (BEC) was obtained for each subject. Blood pressure and its reactivity to noradrenaline and a thromboxane-mimic U46619 were directly measured on day 6 via a catheter implanted in the tail artery of normal and ethanol-treated animals. The mean BEC for each subject correlated with mean arterial blood pressure (MAP); an increase in BEC was associated with a decrease in MAP (p less than 0.02). The mean MAP of subjects with BEC less than 168 mg% was 8% higher than normal (not significant), whereas, the mean MAP of subjects with BEC greater than 182 mg% decreased 27 +/- 4% (p less than 0.01). Conversely, the pressor response to U46619 was markedly enhanced (p less than 0.005) in rats with mean BEC greater than 182 mg% at all doses investigated (12.5-3200 ng per rat). Increases in the pressor response to noradrenaline in ethanol-treated rats were significant only when maximally stimulated by 400 and 800 ng doses (p less than 0.03). A 3-fold increase in sensitivity for U46619 was seen in subjects with high mean BEC, however, sensitivity for noradrenaline did not significantly change. Vasoreactivity was not effected in rats with mean BEC less than 168 mg%. These data demonstrate that a moderate mean BEC for 6 days induces a tendency towards a mild hypertension, whereas, high mean BEC induces marked hypotension which is associated with hyperreactivity. Long-term exposure to high blood ethanol concentrations may predispose the alcohol-dependent rats to hypertensive disease and vasospastic disorders, at least partially, as a result of enhanced sensitivity to prostaglandins such as thromboxane.     

Skeletal muscle vasoconstriction produced by prostaglandin synthesis inhibitors; dependence on pump perfusion

A comparison was made of the effect of prostaglandin synthesis inhibitors (PGSI) on systemic blood pressure and hindlimb muscle vascular resistance of anesthetized dogs under different experimental conditions. When muscle blood flow was monitored using an extracorporeal or noncannulating electromagnetic blood flow probe, indomethacin (5 mg/kg i.v.) increased blood pressure slightly, but did not change vascular resistance. Administration of PGSI (indomethacin, meclofenamate, or naproxen, 5 mg/kg i.v.) after 2 hr of pump perfusion of the hindlimb caused a 22% increase in blood pressure, and 39% increase in vascular resistance 30 min afterwards. When administered immediately after instituting pump perfusion, indomethacin caused no significant change in blood pressure or vascular resistance at the 30 min interval, but at 60 min vascular resistance was increased. A similar vasoconstrictor response to indomethacin was obtained when it was infused in a lower dose intraarterially to the hindlimb, or when given i.v. after ligation of the renal pedicles. The results indicate that pump perfusion results in elaboration of a nonrenal prostaglandin(s) which maintains a vasodilator influence on the skeletal muscle vascular bed.     

Differential regional haemodynamic effects of the non-peptide angiotensin II antagonist, DuP 753, in water-replete and water-deprived Brattleboro rats

Regional haemodynamic effects of DuP 753 were assessed in conscious unrestrained Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturised pulsed Doppler flow probes and intravascular catheters. Responses to DuP 753 were assessed in water-replete animals and in animals following 14h water deprivation to render cardiovascular status dependent on the renin angiotensin system (RAS). In water-replete animals DuP 753 had little effect on mean arterial blood pressure, but there were dose-dependent tachycardias and increases in renal blood flow, associated with vasodilatations. There were also increases in mesenteric blood flow and vascular conductance, but these were not clearly dose-related; DuP 753 had no significant effects on hindquarters haemodynamics. In water-deprived animals DuP 753 caused dose-dependent hypotension, tachycardia, and renal and mesenteric vasodilatations; hindquarters vasodilatation was not dose-dependent. In both conditions, in the presence of DuP 753 (10 mg/kg), captopril had little additional effect. DuP 753 appears to be an extremely effective tool for assessing the role of the RAS in cardiovascular regulation.     

Gastrointestinal blood flow in the red Irish lord, Hemilepidotus hemilepidotus: long-term effects of feeding and adrenergic control

Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 ± 0.6 ml min⁻¹ kg⁻¹ and 4.9 ± 1.3 ml min⁻¹ kg⁻¹, respectively (mean ± SEM, n=7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 ± 18% after 1 day and had a peak increase of 112 ± 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 ± 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 ± 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the α-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant α-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the postprandial increase in gastrointestinal blood flow. Other control mechanisms are suggested. Accepted: 17 November 1999     

Effects of small intestinal glucose load on blood pressure, splanchnic blood flow, glycemia, and GLP-1 release in healthy older subjects

Postprandial hypotension is an important problem, particularly in the elderly. The fall in blood pressure is dependent on small intestinal glucose delivery and, possibly, changes in splanchnic blood flow, the release of glucagon-like peptide-1 (GLP-1), and sympathetic nerve activity. We aimed to determine in healthy older subjects, the effects of variations in small intestinal glucose load on blood pressure, superior mesenteric artery flow, GLP-1, and noradrenaline. Twelve subjects (6 male, 6 female; ages 65-76 yr) were studied on four separate occasions, in double-blind, randomized order. On each day, subjects were intubated via an anesthetized nostril, with a nasoduodenal catheter, and received an intraduodenal infusion of either saline (0.9%) or glucose at a rate of 1, 2, or 3 kcal/min (G1, G2, G3, respectively), for 60 min (t = 0-60 min). Between t = 0 and 60 min, there were falls in systolic and diastolic blood pressure following G2 and G3 (P = 0.003 and P < 0.001, respectively), but no change during saline or G1. Superior mesenteric artery flow increased slightly during G1 (P = 0.01) and substantially during G2 (P < 0.001) and G3 (P < 0.001), but not during saline. The GLP-1 response to G3 was much greater (P < 0.001) than to G2 and G1. Noradrenaline increased (P < 0.05) only during G3. In conclusion, in healthy older subjects the duodenal glucose load needs to be > 1 kcal/min to elicit a significant fall in blood pressure, while the response may be maximal when the rate is 2 kcal/min. These observations have implications for the therapeutic strategies to manage postprandial hypotension by modulating gastric emptying.     

The effects of clonidine on the kidney function in the anesthetized dog

Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increased urine flow. The response of the kidney has been examined in four combinations. The parameters of renal function have been compared during volume expansion by 1.5-2.0% body weight Ringer solution. In the control animals, volume expansion by 2% body weight, resulted in a slight increase in sodium excretion and urine flow. In 10 anesthetized dogs 1.0 microgram/kg/min of clonidine infused i.v. during 30 minutes (the total amount of clonidine infused was 30 micrograms/kg) decreased the arterial blood pressure from 136 +/- 13 mmHg to 127 +/- 12 mmHg and elevated urine flow from 2.95 +/- 1.65 ml/min to 4.34 +/- 1.77 ml/min while the urine osmolality diminished from 399 +/- 107 mosm/l to 265 +/- 90 mosm/l and the glomerular filtration remained constant. In 5 animals 0.1 microgram/kg/min of clonidine was infused into the left renal artery (this dose is corresponding to the renal fraction of the cardiac output) without any effects in the left kidney. 1.0 microgram/kg/min of clonidine infused directly into the left renal artery produced vasoconstriction in the ipsilateral kidney, decreased the glomerular filtration rate and the urine flow. By contrast in the right kidney the urine flow rose without hemodynamic changes, and the urine osmolality became hypoosmotic compared to the plasma. In ten dogs 1.0 microgram/kg/min of clonidine and 1 mU/kg/min of arginine-vasopressin were infused intravenously. The vasopressin infusion superimposed on the clonidine could not inhibit the increase of the urine excretion, and the fall of the urine osmolality. The results suggest that the clonidine increases the renal medullary blood flow possibly via a direct mechanism, decreases the sympathetic outflow to the kidney and via an indirect pathway, mediated by the renin-angiotensin system. The renal medullary flow increase produces a washout of the medullary osmotic gradient, and the water reabsorption diminishes.     

FRUCTOSE PERFUSION IN RAT MESENTERIC ARTERIES IMPAIRS ENDOTHELIUM-DEPENDENT VASODILATION

We demonstrated that the fructose-induced hypertensive rat, representative of the principal metabolic abnormalities found in a majority of hypertensive patients, i.e. hypertriglyceridemia, hyperinsulinemia and insulin resistance (Syndrome X), is associated with an impaired response to endothelium-dependent vasodilators and that fructose may directly contribute to this impairment. Twelve male Wistar rats were divided into two groups, one given 10% fructose (n=6); the other no fructose (n=6) for 40 days in the drinking water. Systolic blood pressure was measured via the tail cuff method. Perfusion pressure responses to acetylcholine, were measured in the isolated perfused mesenteric vascular bed. Constrictor or dilator responses were measured as increases or decreases, respectively, of the perfusion pressure at a constant flow (4 ml/min). Fructose-fed rats had significantly higher blood pressure, insulin and triglyceride levels than control animals. In phenylephrine constricted beds, the endothelium-dependent dilatation to acetylcholine (0.001 to 1 μmol) was attenuated in the fructose-fed group compared to control animals. Whether this abnormality results from the syndromes (hyperinsulinemia, hypertension and hypertriglyceridemia) associated with the fructose-fed animal model is unknown. We therefore hypothesized that fructose can impair the endothelium-dependent vasodilator response. This was evaluated by perfusing mesenteric arteries from normal rats with control mannitol (40 mM) or fructose (40 mM). Endothelium-dependent dilation to acetylcholine was impaired in fructose-perfused mesenteric arteries. Indomethacin restored the vasodilator response to acetylcholine, suggesting that a cyclooxygenase derivative mediates the impaired response. Thus, we conclude that fructose can contribute to the impaired endothelium-dependent response in the fructose-induced hypertensive rat model. Published by Elsevier Science Inc.