Enhancement of resistance to coccidiosis and necrotic enteritis in broiler chickens by dietary muscadine pomace.

Muscadine pomace (MP), a by-product of the production of wine and juice from Vitis rotundifolia, was dried and tested in chickens for effects on primary resistance to coccidiosis, development of protective immunity after vaccination with live coccidia, and resistance to necrotic enteritis (NE) caused by the joint action of Clostridium perfringens and coccidia. To test primary resistance to coccidiosis, 2-wk-old chicks were given 2% or 5% MP in the diet and inoculated with Eimeria acervulina and E. maxima. Birds given MP at either level had significantly (P < 0.05) lower lesion scores at 7 days postinoculation, in comparison with control birds, although weight gains were statistically similar. Broiler chickens were given 2% or 5% MP and grown to 42 days to test the palatability of MP. Birds given 2% MP in feed grew similarly to untreated controls, but birds given 5% had poorer average live weight. This suggested a negative effect on feed intake at the higher level. The effects of dietary 0.5% or 2.0% MP on immune protection were tested after live coccidiosis vaccination in the hatchery. Chicks were removed from each pen at 21 days of age and challenged with E acervulina, E. maxima, and E. tenella. Resistance to infection was improved by MP as suggested by significantly (P < 0.05) lower lesion scores 7 days postchallenge, and improved weight gains in comparison with immunized control birds that did not receive MP. At 42 days of age, birds given MP had higher average live weights than controls, although feed efficiency was not affected. An established model was used to study the effect of MP on NE in broiler chickens. Chicks were inoculated with live coccidia at 14 days of age and dosed orally with live cultures of C perfringens on day 19, day 20, and day 21. Enteritis caused 48% mortality in the first study and 67% mortality in the second study. Dietary MP at 0.5-2.0% significantly (P < 0.05) reduced mortality in both experiments; improved weight gain relative to the unmedicated, infected control; and reduced lesion scores at necropsy. Overall, the results of six experiments suggested that MP given in the diet at 0.5% or higher had a positive effect on primary resistance and development of acquired resistance to two severe intestinal diseases in chickens.

Failure of high fat diets to promote mammary cancers in spontaneously hypertensive rats.

Rat strains differ in their susceptibilities to chemically-induced mammary carcinogenesis. The present study tested the hypothesis that the spontaneously hypertensive rat (SHR) strain is resistant to mammary carcinogenesis. Resistance would imply the presence of the mammary carcinoma suppressor (MCS) gene. Therefore, we also wanted to test the ability of this gene to inhibit mammary tumor promotion in the presence of high fat diets. Female SHRs were treated with DMBA (5 mg/rat) at 50 days of age and transferred to either a 20% corn oil or 19% menhaden oil + 1% corn oil diet one week later. At 17 weeks post-DMBA none of the rats in either group developed mammary carcinomas. Multiple palpable nodules formed in the mammary gland indicating that initiation had occurred. We conclude that the SHR strain is genetically resistant to DMBA-induced mammary carcinogenesis by mechanisms involving a blockade of promotion.

High fish oil diet increases oxidative stress potential in mammary gland of spontaneously hypertensive rats.

1. The purpose of this study was to determine whether high omega-3 (19% menhaden oil, 1% corn oil) or high omega-6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group. 2. We found that the high omega-3 and high omega-6 fatty acid diets did not significantly decrease mean arterial pressure. Marked differences occurred between the effects of omega-3 and omega-6 high fatty acid diets on baseline oxidation, auto-oxidation and iron-ascorbate catalyzed oxidation. The omega-3 diet showed 675% increase in basal oxidation, a 2624% increase in auto-oxidation and a 4244% increase in iron-ascorbate catalyzed oxidation compared to the omega-6 diet in mammary tissue homogenates. Although all rats were given 5 mg DMBA (i.g.), no mammary tumours were observed in any of the dietary groups. 3. We conclude that: (i) high polyunsaturated fatty acid diets do not decrease blood pressure in the female SHR; (ii) high fish oil diet markedly increases oxidative potential in the mammary gland; and (iii) the female SHR is resistant to DMBA-induced tumourigenesis.

Cardiovascular effects of NMDA and MK-801 infusion at area postrema and mNTS in rat.

In urethane-anesthetized male Sprague-Dawley rats, microinfusion of N-methyl-D-aspartate (NMDA) into the area postrema (AP) at the dose of 10 ng produced significant decreases in mean arterial pressure (MAP) (-26 +/- 5 mmHg), heart rate (HR) (-34 +/- 6 bpm), renal blood flow, mesenteric blood flow, and iliac vascular resistance. In addition, microinfusion of the same dosage of NMDA into the medial nucleus tractus solitarius (mNTS) produced significant decreases in MAP (-33 +/- 4 mmHg), HR (-33 +/- 6 bpm), renal blood flow, mesenteric blood flow and vascular resistance, and iliac blood flow and resistance. MK-801 (dizocilpine) microinfusion alone produced no significant changes in MAP or HR when microinfused either into the AP or unilaterally into the mNTS; however, bilateral microinfusion of MK-801 into mNTS produced sustained hypertension and tachycardia, lasting about 30 min. MK-801 pretreatment at both AP and mNTS effectively blocked NMDA-induced cardiovascular responses. MK-801 microinfusion at AP significantly attenuated baroreceptor reflex-mediated bradycardia elicited by intravenous injection of phenylephrine, but did not alter reflex tachycardia elicited by intravenous nitroprusside. In conclusion, NMDA receptor-mediated neurotransmission is involved in the cardiovascular functions of both AP and mNTS. Both loci appear to be sites of action for MK-801.

Effects of total fasting or chronic food restriction on plasma endothelin levels in rats.

We tested the effects of 24- and 48-h fasting and 40% calorie restriction stresses on plasma endothelin (ET)-1,2 levels in male Sprague-Dawley rats. Plasma ET-1,2 levels in pg/ml were lower in 24-h fasted rats (15.48 +/- 3.49), 48-h fasted rats (5.28 +/- 4.32), and in chronically food-deprived rats (R) (10.49 +/- 6.28) compared to ad lib-fed (AL) rats (21.23 +/- 9.38). The R rats were pair-fed 40% fewer calories than AL rats. We conclude that calorie restriction or total food deprivation stress decreases plasma ET-1,2 levels, unlike many other forms of physiological stress that have been shown to increase plasma ET-1,2 levels.

MK-801 affects cardiovascular responses produced by GABAA agents in area postrema.

The cardiovascular effects of nanoliter microinfusions of muscimol, bicuculline, and MK-801 (dizocilpine) into area postrema (AP) were tested in urethane-anesthetized male Sprague-Dawley rats. Microinfusion of muscimol (10 nl/min/5min, 1 ng/nl) into the AP produced significant hypertension (+29 +/- 8 mmHg), but no significant change in heart rate (HR). Microinfusion of bicuculline (10 nl/min/5 min, 1 ng/nl) into the AP produced significant hypotension (-27 +/- 4 mmHg) and bradycardia (-53 +/- 10 bpm). Treatment of the AP with MK-801 (20 nl/min/5 min, 6 ng/nl) produced no changes in mean arterial pressure or HR by itself, but it completely blocked the hypotension and bradycardia produced by bicuculline infusion, without affecting the hypertension produced by muscimol microinfusion into AP. Following pretreatment of AP with MK-801, microinfusion of muscimol into the AP produced significant tachycardia (+51 +/- 16 bpm). The data suggest that a) GABAergic neurotransmission in the AP affects its cardiovascular functions; b) functional interactions between NMDA receptor-mediated neurotransmission and GABAA receptor-mediated neurotransmission within the AP modulate blood pressure and HR regulation.

Glucose turnover in lean and obese rats of the SHR/N-cp and LA/N-cp strains.

1. The relationship between hypertension, obesity, non-insulin-dependent diabetes mellitus and various parameters of glucose metabolism was studied. Lean and obese rats of the SHR/N-cp and LA/N-cp congenic strains were studied at four months of age. 2. Tritium and 14C-labeled glucoses were infused in one set of rats while tritiated water and 14C-labeled alanine were infused in a second group. 3. Glucose oxidation, turnover, conversion to glycogen, fatty acid synthesis, and alanine conversion to glucose were determined, as were blood pressure, pulse pressure and heart rate. 4. The presence of obesity influenced body weight, body fat, de novo fatty acid synthesis, organ weights, glucose mass, glucose oxidation, glucose synthesis, glucose carbon turnover and pulse pressure. 5. It had no effect on glycogen synthesis, tissue glycogen levels, blood glucose, glucose space, or blood pressure. 6. Strain differences were observed in final body weight, organ weights, blood pressure, pulse pressure, hepatic fatty acid synthesis, glucose mass, glucose space, glucose synthesis, liver glycogen levels and glucose conversion to muscle glycogen. 7. Strain-phenotype interaction effects were observed on glucose incorporation into hepatic glycogen, Cori cycle activity, hepatic de novo fatty acid synthesis, final body weight, fat pad weight, heart weight, and mean arterial pressure. 8. These results suggest that although obesity and hypertension are genetic traits in these rats, these traits are independent in their influence on the metabolism of glucose and the development of non-insulin-dependent diabetes mellitus.

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats.

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.

Angiotensin II binding in area postrema and nucleus tractus solitarius of SHR and WKY rats.

The distribution of angiotensin II (AII) binding sites in the area postrema (AP) and adjacent nucleus tractus solitarius (NTS) was compared in spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. 125I[Saralasin-1-Isoleucine8]-Angiotensin II (125I[SI]-AII) binding density was quantitated from autoradiographic images by computer-assisted image analysis. Seventeen 30 microns serial coronal sections inclusive of the entire AP were analyzed as either individual sections or as groups of sections designated as caudal, middle, or rostral area postrema regions. 125I[SI]-AII binding density was greatest in caudal AP and declined progressively in the rostral direction in both strains; however, binding density in SHR was significantly higher than in WKY rats at each level of the AP analyzed. 125I[SI]-AII binding in the entire area postrema was approximately 46% higher in SHR rats. In the NTS, however, there were no differences in binding density between strains. At the middle level of the AP, 125I[SI]-AII binding was highest in the ventral midline and lowest in the dorsolateral region. In the NTS, the highest 125I[SI]-AII binding density was found in the pars commissuralis and pars medialis. In conclusion a) 125I[SI]-AII binding density was nonhomogeneous in the AP and NTS of both strains, b) qualitatively similar patterns of nonhomogeneity of binding in the AP and NTS were noted in both strains; however, c) the SHR strain consistently had higher density AII binding than WKY in AP, but not in NTS.

Life span is shortened in BHE/cdb rats fed a diet containing 9% menhaden oil and 1% corn oil.

The effects of feeding 2 or 10% fat on glucose tolerance, blood lipids, life span and tissue pathology of male BHE/cdb rats were studied. Six groups of 30 rats were fed from weaning diets containing 1% corn oil plus either 1 or 9% corn oil (CO diets). Animals that became ill and died were necropsied and their tissues were examined histologically. Glucose tolerance and blood lipids were determined at 300 and 600 d of age. At 300, 500, 600 and 700 d of age subsets of rats were killed and heart, aorta, lungs, liver, pancreas and kidneys collected for histological examination. The experiment was terminated at 700 d. Feeding the high level MO or BT diet delayed the development of glucose intolerance and lipemia. Longevity was shorter in the rats fed the high MO diet. There were few differences among the groups of rats fed the 2% fat diets with respect to glucose tolerance and lipemia. Glomerulosclerosis was observed in all rats but was more severe and appeared earlier in rats fed the high MO diet than in those fed the high CO or BT diets. In rats with severe renal lesions, mineralized foci were observed in soft tissue, notably the aorta and heart. The results of this study indicate that the source and amount of the dietary fat can influence age-related tissue changes and longevity.

Area postrema stimulation induces differential renal hemodynamics with two anesthetics.

The effect of area postrema stimulation (APS) on blood pressure, renal blood flow (RBF), and renal vascular resistance was compared in urethan-anesthetized and pentobarbital sodium-anesthetized Sprague-Dawley rats. Mean arterial pressure (MAP) increased in a frequency-dependent manner during APS in both urethan- and pentobarbital-anesthetized rats. Although no significant differences occurred in the maximum percent change in MAP between groups, marked differences occurred in RBF and calculated renal vascular resistance (RVR) changes. In urethan-anesthetized rats, RBF and MAP increased during APS, but RVR did not change. In contrast, APS significantly decreased RBF (-26.5 +/- 1.9%) while increasing RVR (+99.4 +/- 11.4%) in pentobarbital-anesthetized rats. The increase in RVR in the pentobarbital-anesthetized group during APS was eliminated by prior ganglionic blockade. It was concluded that the anesthetic agent employed can significantly alter the degree to which APS can activate renal vasomotion in the rat.

Systemic glutamate induces degeneration of a subpopulation of serotonin-immunoreactive neurons in the area postrema of rats.

Neuronal damage in the area postrema (AP) of adult Sprague-Dawley rats was induced by subcutaneous administration of monosodium glutamate (MSG; 9 mg/g b.wt.). Serotonin-immunoreactive (5-HT-IR) neurons were visualized in the AP 3 h or 7 days after control or MSG treatment. At 3 h post MSG, many 5-HT-IR neurons showed morphological signs of degeneration, such as, cytoplasmic vacuolization, chromatin clumping and dendritic hypertrophy. MSG treatment caused a 30% reduction of detectable AP 5-HT neurons after 7 days. We conclude that a subpopulation of serotonergic neurons in the AP is sensitive to the neuroexcitotoxic effect of systemic glutamate.

Interactive effect of body posture on exercise-induced atrial natriuretic peptide release.

The purpose of this investigation was to test the hypothesis that supine exercise elicits a greater atrial natriuretic peptide (ANP) response than upright exercise because of higher atrial filling pressure attained in the supine posture. Plasma ANP concentration ([ANP]) was measured during continuous graded supine and upright exercise in eight healthy men at rest after 4 min of cycling exercise at 31, 51, and 79% of posture-specific peak oxygen uptake (VO2 peak), after 2 min of cycling at posture-specific VO2 peak, and 5 and 15 min postexercise. [ANP] was significantly increased (P less than 0.05) above rest by 64, 140, and 228% during supine cycling at 51 and 79% and VO2 peak, respectively. During upright cycling, [ANP] was significantly increased (P less than 0.05) at 79% (60%) and VO2 peak (125%). After 15 min of postexercise rest, [ANP] remained elevated (P less than 0.05) only in the supine subjects. [ANP] was 63, 79, and 75% higher (P less than 0.05) in the supine than in the upright position during cycling at 51 and 79% and VO2 peak. Systolic, diastolic, and mean blood pressures were not significantly (P greater than 0.05) different between positions in all measurement periods. Heart rates were lower (P less than 0.05) in the supine position compared with the upright position. In conclusion, these results suggest that supine exercise elicits greater ANP release independent of blood pressure and heart rate but presumably caused by greater venous return, central blood volume, and concomitant atrial filling pressure and stretch.

Systemic glutamate induces degeneration of a subpopulation of tyrosine hydroxylase-immunoreactive neurons in the rat area postrema.

Neuronal damage in the area postrema (AP) of 12-14-week-old male rats was induced by subcutaneous administration of monosodium glutamate (MSG). An immunocytochemical method was used to visualize catecholaminergic neurons in the AP after MSG-treatment. Some tyrosine hydroxylase-immunoreactive neurons exhibited marked signs of degeneration, while others appeared undamaged. We conclude that catecholamine-synthesizing neurons in the AP are differentially sensitive to the neuroexcitotoxic effect of systemic glutamate.

Plasma concentrations of immunoreactive atrial natriuretic peptide in hospitalized cirrhotic and noncirrhotic patients: evidence for a role of deficient atrial natriuretic peptide in pathogenesis of cirrhotic ascites.

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.

Effects of therapeutic paracentesis on systemic and hepatic hemodynamics and on renal and hormonal function.

Thirteen patients with cirrhosis and tense ascites (six with and seven without peripheral edema) underwent 4- to 15-liter paracentesis without intravenous "colloid" replacement. Cardiac output increased from 6.6 +/- 0.7 liters per min at baseline to 8.2 +/- 0.7 liters per min (p less than 0.003) 1 hr after large-volume paracentesis completion and fell to 7.5 +/- 0.69 liters per min (p less than 0.05 vs. baseline, p less than 0.02 vs. 1 hr) 24 hr after large-volume paracentesis completion. There was no change in mean arterial pressure or mean pulmonary artery pressure. Central venous pressure fell from 9.1 +/- 0.8 mm Hg at baseline to 8.6 +/- 1.4 mm Hg 1 hr post-large-volume paracentesis to 6.8 +/- 1.0 mm Hg (p less than 0.005 vs. baseline, p less than 0.02 vs. 1 hr value) at 24 hr, and pulmonary capillary wedge pressure fell from 13.1 +/- 0.9 to 11.1 +/- 1.3 mm Hg 1 hr after large-volume paracentesis and to 9.89 +/- 1.2 (p less than 0.01 vs. baseline, p less than 0.03 vs. 1 hr after large-volume paracentesis) at 24 hr. Heart rate fell from 90 +/- 3.0 to 85 +/- 2.9 beats per min (p less than 0.01) 1 hr after large-volume paracentesis completion, but increased to 89 +/- 2.5 beats per min (p less than 0.02 vs. 1 hr after large-volume paracentesis) at 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

The median preoptic area in cardiovascular reflex activity.

Two examples are used to illustrate the flexibility within the central servocontrol system that regulates blood volume and blood pressure. The variations are seen in the modification of components directed both towards short-term and long-term control. The preferential circuit used in the servocontrol system can and does change. The interaction of baromechanisms with cerebellar-fastigial activation selectively engages sympathetic output to the kidney resulting in an enhanced release of renin that is disproportional to the rise in renal vascular resistance. The cerebellar component adds a feature to the reduction in vascular conductance that when fully developed increases vascular volume. The permissive role of sites in the anteroventral hypothalamus suggests a neural loop that, when absent, not only allows the sympathetic activity to run unabated but fails to prevent a tachycardia state or to develop a bradycardia in response to a rise in arterial pressure. The latter may be a transient feature not persisting for more than a day. However, when compared to the normal responses of the paired sham controls, such a change is taken as an example of dynamic shift in preferential pathways.

The angiotensin II pressor system of the rat forebrain.

An anterior hypothalamic knife cut that leaves intact two central sites of action of angiotension II produces the same deficits in the pressor responses to angiotensin II that have been attributed to destruction of two circumventricular organs (the subfornical organ and the organum vasculosum of the lamina terminalis). The central pressor actions of angiotensin II are necessary for the full expression of renin-dependent renal hypertension. The anterior hypothalamic knife cut attenuates renin-dependent aortic ligation hypertension. It has been shown that electrolytic destruction more anterior to this knife cut, in the anteroventral 3rd ventricle region, also attenuates two forms of renin-dependent hypertension, aortic ligation hypertension and two-kidney Goldblatt hypertension in the rat. Electrolytic lesions in the subfornical organ also reduce renin-dependent, two-kidney Goldblatt hypertension. These data are consistent with the hypothesis that a common efferent system from the organum vasculosum of the lamina terminalis and subfornical organ mediates the central pressor response to angiotensin II and is involved in the development of renin-dependent hypertension. A model is proposed for the circuitry in the rat forebrain that is involved in the pressor response to angiotensin II.