Biomedical subjects

N Emmett

Publications and source records attributed to N Emmett.

At least 19 recordsLinked to original sources

PubMed2005

Alterations in aldosterone and angiotensin II levels in salt-induced hypertension.

Several studies have demonstrated that plasma renin-angiotensin activity is reduced in rats administered a high salt diet. We evaluated changes in plasma and tissue levels of aldosterone (ALDO) and angiotensin II (A-II), as well as the reduced-to-oxidized glutathione ratio. Male Dahl salt-sensitive (SS) rats were placed on either a high-salt (8% NaCl; HS) or a normal-salt (0.3% NaCl; NS) diet for 3 weeks. Prior to and weekly on the diets, systolic blood pressure was measured by tail cuff plethysmography. Levels of A-II and ALDO in plasma, heart, and kidney were analyzed by enzyme immunoassay. Reduced and oxidized gluthatione were simultaneously measured by HPLC fluorescence detection. Heart and kidney tissues were prepared for histological analysis. Systolic blood pressure in animals on a HS diet was significantly elevated above that of those on a NS diet. High salt caused a reduction in both plasma A-II and ALDO levels; while their levels in the heart and kidney were increased. Exposure to a high-salt diet led to the enlargement of both heart and kidney. The reduced-to-oxidized glutathione ratio in plasma, heart and kidney was lowered by exposure to a HS diet. Kidneys from animals on a high-salt diet showed fibroid necrosis associated with wrinkling and thickening of the glomerular capillary wall, while hearts were hypertrophic. Taken together, high dietary salt induces inappropriate activation of the local renin-angiotensin-aldosterone systems. Tissue levels of angiotensin II and aldosterone may be more reflective of the severity of vascular maladaptations than are plasma levels, and may play a greater role in the maintenance of hypertension.

Aldosterone↗

PubMed2003

NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats.

The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

Animals↗

PubMed2001

Gender differences in the attenuation of salt-induced hypertension by angiotensin (1-7).

Chronic infusion of angiotensin (1-7) [Ang-(1-7)] lowers blood pressure in spontaneously hypertensive rats (SHR). To assess the role of Ang-(1-7) in salt-induced hypertension, Ang-(1-7) (24 microg/kg/hr) or saline was administered chronically via osmotic minipump into the jugular vein of 5-6 wk-old male (M) and female (F) Dahl salt-sensitive rats placed on a high-salt (8% NaCl) diet for 2 weeks. Blood pressure (BP) and heart rate were measured prior to the start of the diet and weekly thereafter. Ang-(1-7) significantly attenuated the BP increase after 1 wk on the diet in both M and F rats, but after 2 weeks only in F rats. Enhanced release of prostacyclin, (6-keto PGF1 alpha), following Ang-(1-7) treatment was observed in both M and F rats. In addition, significant increases in aortic blood flow and plasma levels of nitric oxide were observed in the F rats following Ang-(1-7) treatment. These findings demonstrate that the reduction in BP is due to both prostacyclin and NO and that there is a gender difference in the attenuation of salt-induced hypertension by Ang-(1-7).

6-Ketoprostaglandin F1 alpha↗

PubMed2001

L-NAME, a nitric oxide synthase inhibitor, as a potential countermeasure to post-suspension hypotension in rats.

A large number of astronauts returning from spaceflight experience orthostatic hypotension. This hypotension may be due to overproduction of vasodilatory mediators, such as nitric oxide (NO) and prostaglandins. To evaluate the role of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we assessed the cardiovascular responses and vascular reactivity to 7-day 30 degrees tail-suspension and a subsequent 6 hr post-suspension period in conscious rats. After a pre-suspension reading, direct MAP and heart rate (HR) were measured daily and every 2 hrs post-suspension. The NO synthase inhibitor L-NAME (20 mg/kg, i.v.), or saline, were administered after the 7th day reading prior to release from suspension and at 2 and 4 hrs post-suspension. At 6 hrs post-suspension, vascular reactivity was assessed. While MAP did not change during the suspension period, it was reduced post-suspension. Heart rate was not significantly altered. L-NAME administration reversed the post-suspension reduction in MAP. In addition, the baroreflex sensitivity for heart rate was modified by L-NAME. Thus, the post-suspension reduction in MAP may be due to overproduction of NO and altered baroreflex activity.

Animals↗

PubMed2001

Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer.

The actin cytoskeleton is the key cellular machinery responsible for cellular movement. Changes in the organization and distribution of actin and actin binding protein are necessary for several cellular processes such as focal adhesion formation, cell motility and cell invasion. Here we examined differences in cytoskeletal protein distribution, cell morphometry and cell motility of metastatic and non-metastatic cells. Correlations were found between metastatic potential phenotypic properties such as cell motility, cell spreading and cytoskeletal organization in prostate cancer. As a cell progresses from a normal state to a malignant state, it loses its ability to function normally and also become poorly differentiated. Differentiation therapy is concerned with the redirection of malignant cells toward a terminal, non-dividing state using non-cytotoxic agents. Two well acknowledged differentiation agents, retinoic acid (RA) and diflouromethylomithine (DFMO) were examined for their ability to alter cellular phenotypes associated with metastatic potential in rat prostate cancer cell lines. The results of these studies indicate that there are sub-cellular differences between non-metastatic and highly metastatic cells relative to cytoskeletal organization. We also show that treatment of highly metastatic cells with either RA or DFMO significantly alters cell morphology, cell morphometry and motility to states similar to non-metastatic cells.

Actins↗

PubMed2001

Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats.

Orthostatic hypotension is a serious condition that is sometimes manifested in astronauts during standing postflight. These observations may be related to impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. To evaluate the role of the cyclooxygenase inhibitor indomethacin as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-hr post-suspension period in conscious male Sprague-Dawley rats. Indomethacin (2 mg/kg) or saline were administered intravenously prior to release from suspension and at 2 and 4 hrs post-suspension. Direct MAP and heart rate were determined prior to suspension, daily and every 2 hrs post-suspension. During suspension, MAP did not change, in contrast, during post-suspension; it decreased compared to parallel non-suspended, untreated animals. There were no significant changes in heart rate. The reduction in MAP post-suspension was associated with significant increases in plasma prostacyclin. Indomethacin attenuated the observed post-suspension reduction in MAP and reduced plasma prostacyclin levels. Also, the baroreflex sensitivity for heart rate was modified by indomethacin--the MAP threshold for baroreflex activation was raised and the effective MAP range expanded. Thus, the post suspension reduction in mean arterial pressure may be due to overproduction of vasodilatory prostaglandins and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

Animals↗

PubMed2000

Cardiovascular responses to simulated microgravity in Sprague-Dawley rats.

Microgravity is known to induce orthostatic intolerance and baroreflex impairment in astronauts. Cardiovascular responses observed in 30 degrees head-down tilt rat models, whether 24 hr whole body suspension (WBS) or 7 day tail-suspension (TS), mimic observations made during exposure to microgravity. We evaluated the cardiovascular effects of simulated microgravity and the subsequent post-suspension in rats using the above models. Mean arterial pressure (MAP) of both WBS and TS rats did not change during suspension. In both models, MAP decreased post-suspension and this response lasted for 6 hrs. Salt-loaded animals did not show a post-suspension reduction in MAP. Plasma ionized calcium was decreased at 2 hr of WBS, with no change in sodium, potassium, magnesium, glucose, or hematocrit. Body weight changes were similar for all animals whether under suspension or control conditions. Both rat models demonstrate post-suspension hypotension and these results support the notion that salt-loading may have some beneficial effects in ameliorating this hypotension.

Animals↗

PubMed2000

Salt-loading and simulated microgravity on baroreflex responsiveness in rats.

Cardiovascular adaptations observed during exposure to microgravity results in impairment of baroreflex activity partially as a result of fluid and electrolyte shifts. The head-down tilt rat model mimics some of the physiological observations that have been made in astronauts. We examined the effects of salt-loading on baroreflex activity after 7 day simulated microgravity (30 degrees tail-suspension) and the subsequent 6 hr post-suspension in Sprague-Dawley (SD) rats, using low salt (0.3% NaCl) and high salt (8% NaCl) diets. In suspended animals on a low salt diet, the baroreflex response curve was shifted to the left, while the heart rate (HR) range and MAP50 values were reduced compared to their parallel tethered, non-suspended controls. For non-suspended animals, salt-loading shifted the curve to the right with a reduced HR range. In salt-loaded, suspended animals, the curve and its parameters resemble those of non-suspended animals on a low salt diet. In summary, these data have demonstrated that a short-term (seven days) simulated weightlessness may elicit cardiovascular deconditioning in rats after release from the simulation manifested as an altered responsiveness in baroreceptor-heart rate reflex and a lowered blood pressure while the rats are tethered and horizontal. Our results also suggest the counteracting effect of salt loading on cardiovascular deconditioning.

Animals↗

PubMed1999

Enhanced nitric oxide synthesis reverses salt-induced alterations in blood flow and cGMP levels.

To understand the role of nitric oxide in salt-induced hypertension, we evaluated cardiovascular, hemodynamic and biochemical parameters in Dahl salt-sensitive rats fed low (0.3%) and high (8.0%) sodium diets. Two high salt groups received 1.25 and 2.5 g/L l-arginine in their drinking water. After three weeks of treatment, blood pressure was greater in the high salt groups. l-arginine did not modify salt-induced hypertension. Eicosapentaenoic acid (EPA) caused a smaller depressor response compared to normotensive rats. The increase in blood pressure was associated with decreases in aortic and renal blood flows. In renal artery, the reduction was counteracted by both l-arginine doses; whereas in the aorta, only the higher l-arginine one restored blood flow. The salt-induced reduction in aortic cyclic GMP level was only overcome by the higher l-arginine treatment. These data suggest that at the dose levels tested, nitric oxide reverses the reduction in cGMP and blood flow, but not the blood pressure changes associated with salt-induced hypertension.

Animals↗

PubMed1999

Angiotensin-(1-7) antagonist [D-Ala7-Ang-(1-7);A-779] attenuates post-suspension hypotension in Sprague-Dawley rats.

Cardiovascular deconditioning manifested by reduction in mean arterial pressure (MAP) and cardioaccleration are usually observed in astronauts during standing postflight. The head-down tilt (HDT) rat model with "unloaded" hindlimbs has been extensively studied because some of the observed responses mimic observations made during exposure to microgravity. Angiotensin-(1-7) is a biologically active component of the renin-angiotensin system that acts to oppose the pressor and proliferative actions of Angiotensin II. It produces a hypotensive response by either stimulating production of vasodilator prostaglandins (i.e., prostacyclin), increasing nitric oxide or both. In the present study, we have evaluated the role of a specific inhibitor of Ang-(1-7), D-Ala7-Ang-(1-7)[A-779], as a countermeasure against post-suspension hypotension.

Angiotensin II↗

PubMed1999

Influence of simulated microgravity on cardiovascular and hemodynamic parameters in Dahl salt-sensitive rats.

Prolonged exposure to microgravity, in humans, induces cardiovascular deconditioning and impairment of baroreflex activity partially as a result of fluid and electrolyte shifts. Animal models of simulated microgravity have been developed to mimic the above responses. We examined the effects of both 24 hr whole body suspension and 7 day tail-suspension and the subsequent 6 hr post-suspension in salt-loaded (2 wks on 8% NaCl diet) Dahl salt-sensitive rats. In both models, mean arterial pressure (MAP) and heart rate (HR) were unchanged during the suspension period. Upon release from suspension, there was no difference in the MAP or HR responses. Blood flows measured in the lower abdominal aorta and renal artery were not different between suspended and control animals. In both models, there was a similar body weight reduction in all groups. MAP responses to both phenylephrine (PHE) and sodium nitroprusside (SNP) were not affected by simulated microgravity. The HR response to SNP in suspended animals was greater than that of control animals; whereas, PHE-induced responses were not different. These data support the notion that simulated microgravity did not alter the MAP responses to SNP and PHE, however, HR responses were enhanced by SNP in the salt-loaded Dahl rats. In addition, salt-sensitivity/salt-loading prevents the reduction in MAP observed post-suspension in normotensive rats.

Animals↗

PubMed1998

Possible mechanisms of salt-induced hypertension in Dahl salt-sensitive rats.

Genetic factors, diet, and salt sensitivity have all been implicated in hypertension. To further understand the mechanisms involved in salt-induced hypertension, cardiovascular, hemodynamics, and biochemical parameters in Dahl salt-sensitive rats were evaluated in animals on high- and low-sodium diets. During a 4-week treatment period, blood pressure was significantly elevated in the high (8.0%) salt group compared to the low (0.3%) salt group (p< or =0.05 for weeks 2 and 4, respectively). No significant changes were observed in heart rate. The increase in blood pressure was associated with significant increases in lower abdominal aortic and renal vascular resistance, along with a reduction in blood flow. A fourfold increase in arginine vasopressin was observed in animals on the high-salt diet. In contrast, there was no effect on plasma sodium, potassium, or aldosterone levels during the treatment period. As measured in isolated aortic rings, the high-salt diet also caused a significant elevation in stimulated norepinephrine release and a reduction in cyclic GMP levels. These data suggest that salt-induced elevation in blood pressure is due to activation of both the sympathetic and arginine vasopressin systems via mechanisms involving decreased cyclic GMP generation in vascular smooth muscle.

Aldosterone↗

PubMed1994

Biometric assessment of prostate cancer's metastatic potential.

Currently, no protocol exists that can assess the metastatic potential of prostate adenocarcinoma. The reason for this is partly due to the lack of information on cellular changes that result in a tumor cell's becoming metastatic. In this investigation, attempts were made to devise a method that correlated with the metastatic potential of AT-1, Mat-Lu, and Mat-LyLu cell lines of the Dunning R-3327 rat prostatic adenocarcinoma system. To accomplish this, we applied BioQuant biometric parameters, i.e., area, shape factor, and cell motility. AT-1 had a lower shape factor and a greater area as compared with the more highly metastatic Mat-Lu subline. No significant difference in area or shape factor was detected between the AT-1 cell line and the highly metastatic Mat-LyLu line. However, the lowly metastatic AT-1 line had less motility as compared with the Mat-Lu and Mat-LyLu lines. This study revealed that metastatic potential could be partially predicted via area and shape factor and accurately predicted via cell motility.

Adenocarcinoma↗

PubMed1993

Adhesion and invasion potential of rat prostatic cancer cells: correlation with metastatic potential.

This investigation examined the ability of low-metastatic AT-1 and high-metastatic ML and MLL cell lines to adhere to a monolayer of bovine aortic endothelial cells and fibronectin substratum and penetrate a matrigel basement membrane matrix. Cell area, shape factor, and motility as influenced by fibronectin were also examined using these cell lines. The ability of these cells to adhere to fibronectin and traverse matrigel matrix correlated with their metastatic potential. In addition, fibronectin increases cell circularity and reduces cell area as metastatic potential increases within AT-1 to ML or MLL cell lineages.

Animals↗

PubMed1992

Influence of low density lipoproteins on vascular smooth muscle cell growth and motility: modulation by extracellular matrix.

Low density lipoproteins (LDL) are thought to play a major role in cardiovascular diseases such as atherosclerosis. Much remains to be done to understand the cellular effects of LDL and how the extracellular matrix (ECM) influences these effects. We found that LDL produced a dose dependent increase in vascular smooth muscle cell (SMC) proliferation. The ECM altered the proliferative response of SMC to LDL: on collagen I there was a 66% inhibition, endothelial cell derived-ECM a 2-fold increase, and collagen IV no difference in proliferation compared to paired controls. LDL affected SMC motility (cell area and shape factor) but the extent and direction of the effect depended on whether the cells were cultured on uncoated or coated dishes. LDL treated cultures had a 5-fold lower migration rate but net movement was not different, suggesting that LDL decreased SMC random movement. There was a dose-dependent accumulation of lipid by SMC incubated with LDL and, subsequently, cytoplasmic lipid droplets were observed. Cells cultured on uncoated plates showed an increased cholesterol content as a function of LDL concentration. In contrast, cells cultured on a collagen IV matrix showed no net change in cholesterol content over the range of LDL concentrations studied. Hence, the uptake of LDL cholesterol appears to be completely inhibited by this matrix. These studies indicate that the influence of LDL on several SMC parameters is modulated by ECM components.

Cell Division↗

PubMed1987

Characterization of purified rabbit uterine renin: influence of pregnancy on uterine inactive renin.

Using specific antibody raised against renal renin, we have documented that the majority of the uterine renin-like activity in gravid and nongravid uteri is immunoreactive renin. To characterize its physiochemical properties, we obtained highly purified uterine renin by two affinity chromatographic steps, pepstatin and antirenin. Uterine renin has a pH optimum of 6, an apparent mol wt of 38K, and a Km of 1.7 microM for homologous substrate. These properties are identical to those of renal renin and are not influenced by the pregnant state. In the basal state, an inactive form of the uterine enzyme constitute 55 +/- 10% of the total uterine renin. During pregnancy, active renin increased 40-fold as inactive renin fell to 4 +/- 3% of the total renin concentration. The renal renin concentration fell as plasma renin increased during pregnancy. These data suggest that the increased uterine renin concentrations during pregnancy are probably due to increased local production and conversion of renin precursor to the active enzyme. This stimulation of the uterine renin level appears to be independent of renal renin.

Animals↗

PubMed1986

Activation of chicken liver fructose- 1,6-bisphosphatase by oxidized glutathione.

Treatment of chicken liver fructose- 1,6-bisphosphatase with oxidized glutathione (GSSG) leads to an increase in activity. This activation is markedly enhanced if treatment is performed in the presence of AMP or Mn2+. The effects of AMP and Mn2+ appear to be synergistic. The maximal activation is over 13-fold and is accompanied by the disappearance of 4 sulfhydryl groups per molecule of enzyme. Both fructose 1,6-bisphosphate and fructose 2,6-bisphosphate can largely prevent this activation. Activation can be reversed by dithiothreitol or cysteine. It appears that GSSG activates this enzyme by thiol/disulfide exchanges with the enzyme's specific sulfhydryl groups.

Adenosine Monophosphate↗

PubMed1980

Identification of renin and renin-like enzymes in rat brain by a renin-specific antibody.

1. The major angiotensin I-generating activity of rat brain extracts has a pH optimum different from that of renal renin and is not inhibited by renin specific antibody. 2. Affinity chromatography utilizing renin specific antibody, pepstatin and alpha-casein yielded fractions that resembled renal renin more closely with respect to antibody inhibition and pH optimum as well as an absence of the ability to hydrolyse haemoglobin. 3. We conclude that rat brain contains a host of enzymes with angiotensin I-generating activity including acid and neutral proteases and an enzyme with the immunochemical identity of renal renin. The biosynthetic origins of this renin-like protein remain uncertain.

Angiotensin I↗