Biomedical subjects

M A Bayorh

Publications and source records attributed to M A Bayorh.

At least 19 recordsLinked to original sources

PubMed2003

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats.

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

6-Ketoprostaglandin F1 alpha↗

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

The role of gender in salt-induced hypertension.

To evaluate gender differences in salt-induced hypertension, female and male Dahl salt-sensitive rats were fed high (8.0% NaCl, HS) and low (0.3% NaCl, LS) salt diets. During a 3-week treatment period, blood pressure was significantly elevated in both female and male HS groups compared to their respective LS groups. The blood pressure and 4 week mortality rate of the female HS group, however, were significantly lower than those of the male HS group. Renal and aortic blood flows were reduced in male rats on HS diet compared to the LS group, while, in females, renal blood flow was elevated and aortic flow was maintained while on HS diet. Plasma prostaglandin E2 and prostacyclin levels were higher in females than males and unaffected by diet. In contrast, plasma nitric oxide levels were reduced by HS, regardless of gender. In isolated aortic rings, HS diet caused a smaller elevation in the stimulated norepinephrine release ratio in female rats than in males. Thus, salt-induced hypertension is associated with a reduction in levels of nitric oxide regardless of gender. Plasma prostaglandin E2 and prostacyclin levels were higher in females. Taken together, the higher plasma prostaglandin levels and reduced sympathetic activity in females may be contributing factors in their lower blood pressure and reduced mortality.

Animals↗

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

The calciuric response to dietary salt of Dahl salt-sensitive and salt-resistant male rats.

BACKGROUND: There are conflicting reports regarding the effect of salt sensitivity on the calciuric response to salt, perhaps because of gender differences and different modes of salt administration. We tested the hypothesis that the calciuric response to dietary salt would not differ for male Dahl salt-sensitive (S) and salt-resistant (R) rats. METHOD: S and R rats were fed high- (80 g/kg) or low- (3 g/kg) salt diets for 3 weeks and urine (24 hour) was collected weekly. RESULTS: Urinary calcium excretion was up to 20-fold greater for S and R rats fed a high-salt diet (P < 0.001) than for S and R rats fed a low-salt diet and did not differ significantly between S and R rats. S rats, however, excreted calcium in significantly higher urine volumes (P< 0.001) during high salt intake and developed hypertension. Plasma parathyroid hormone concentrations of S and R rats did not differ during low salt intake and increased significantly to the same concentration after 3 weeks of high salt intake. CONCLUSIONS: We have previously reported that plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations of male S rats, but not male R rats, were drastically reduced by 3 weeks of high salt intake. These data suggest that salt-induced hypertension and salt-induced alterations in the vitamin D endocrine system of male S rats do not affect the calciuric response to dietary salt.

Animals↗

PubMed2001

The calciuric response to dietary salt of Dahl salt-sensitive and salt-resistant female rats.

BACKGROUND: We have shown previously that the calciuric response to salt does not differ in Dahl salt-sensitive (S) and salt-resistant (R) male rats. Clinical studies with women, however, suggest an effect of salt sensitivity on the calciuric response to salt. The objective of this study was to determine whether there is an effect of salt sensitivity on the calciuric response to salt of female S and R rats. METHOD: Dahl S and R female rats were fed high- (8%) or low- (0.3%) salt diets for 3 weeks. The rats were placed in metabolic cages for 24-hour urine collection at baseline and weekly (for sodium and calcium determination). RESULTS: Blood pressure of female S rats was 177+/-3.0 mm Hg at week 3 of high salt intake compared with 96+/-1 mm Hg for female R rats. Female S rats excreted significantly more calcium than female R rats at baseline (P < 0.001), when fed a nonpurified diet, and during high salt intake (P = 0.004). Salt sensitivity significantly increased calcium excretion, water intake, and urine output when rats were fed a high-salt diet. Calcium excretion, water intake, and urine output of female S rats were time-dependent during high salt intake. Plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations were markedly lower in female S rats fed a high-salt diet, but not in female R rats. Plasma parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not significantly differ between female S and R rats, but plasma concentrations of these two hormones at week 3 were significantly higher in S rats fed a high-salt diet compared with S rats fed a low-salt diet. CONCLUSIONS: Our data indicate that the calciuric response to salt is greater in female S compared with female R rats, thus supporting findings on the effect of salt sensitivity reported in several clinical studies with women. The greater calciuric response to salt of female S rats compared with female R rats, which was not seen in a previous study when male S rats were compared to male R rats, suggest a gender difference in the calciuric response to salt.

Animals↗

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↗

PubMed1998

Plasma 25-hydroxyvitamin D concentrations are inversely associated with blood pressure of Dahl salt-sensitive rats.

Dietary salt is a contributing factor to the development of hypertension in individuals who are salt-sensitive. The vitamin D endocrine system has been reported to modulate vascular structure and function. Since elderly hypertensive females with low plasma renin activity, typical of salt-sensitivity, had significantly lower 25-hydroxyvitamin D concentrations compared with normotensive elderly and young females, we have used Dahl salt-sensitive and salt-resistant rats fed high (80 g/kg diet) and low (3 g/kg diet) salt diets as models to examine the relationship between salt-sensitivity and 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D. Plasma 25-hydroxyvitamin D concentrations of salt-resistant rats were unaffected by a high salt diet, but plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats were significantly reduced within three weeks to lower than 25%. There was a negative association between plasma 25-hydroxyvitamin D concentrations of salt-sensitive rats and the number of days that the rats were fed a high salt diet (r = -0.98, P < 0.02) and a positive association between blood pressure and the number of days that the rats were fed a high salt diet (r = 0.97, P < 0.05). An inverse relationship was found between plasma 25-hydroxyvitamin D concentrations and blood pressure (r = -0.99, P < 0.01). Spontaneously hypertensive rats did not have low plasma 25-hydroxyvitamin D concentrations, suggesting that reduction of plasma 25-hydroxyvitamin D concentration might be specific to salt-induced hypertension.

Animals↗

PubMed1998

Exogenous 25-hydroxycholecalciferol does not attenuate salt-induced hypertension.

We have reported that an inverse relationship exists between blood pressure and plasma concentration of 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, for Dahl salt-sensitive rats fed a high salt diet. Plasma 25-hydroxyvitamin D concentrations decreased with time on the diet, as blood pressure increased. Experiments were conducted to determine whether the blood pressure increase of salt-sensitive rats fed a high salt diet could be attenuated by exogenous 25-hydroxycholecalciferol. Dahl salt-sensitive rats were fed a high salt diet and administered exogenous 25-hydroxycholecalciferol via subcutaneously implanted Alzet pumps. Exogenous 25-hydroxycholecalciferol (various doses from 28 to 80 microg/kg body weight-day) had no significant effect on the blood pressure of vitamin D-replete rats fed a high salt diet for 15 days. When exogenous 25-hydroxycholecalciferol (28 and 60 microg/day-kg body weight) was administered to vitamin D-depleted salt-sensitive rats, plasma 25-hydroxyvitamin D concentrations of the rats fed a low salt diet (26 +/- 2 and 59 +/- 6 nM) were proportional to the 25-hydroxycholecalciferol concentration in the pumps. Plasma 25-hydroxyvitamin D concentrations of the rats fed a high salt diet (18 +/- 1 and 23 +/- 3 nM) were not proportional to the 25-hydroxycholecalciferol concentration in the pumps, but were inversely proportional to the blood pressure of the rats. These data indicate no ameliorating effect of exogenous 25-hydroxycholecalciferol on salt-induced hypertension, but accelerated metabolism and/or clearance of 25-hydroxycholecalciferol in salt-induced hypertension.

Animals↗

PubMed1997

Cardiovascular effects of oxymetazoline and UK14,304 in conscious and pithed rats.

Relatively selective alpha 2-adrenoceptor agonists have proven useful in a variety of therapeutic situations including hypertension, glaucoma and withdrawal from opiate addiction. In particular, oxymetazoline (OXY) and UK14,304 (UK) have been used in subclassifying alpha 2-adrenoceptors and imidazoline receptors. We evaluated the cardiovascular effects of OXY and UK in conscious and pithed rats in the presence and absence of efaroxan (EFA), idazoxan (IDA) and rauwolscine (RAU). Both OXY or UK (1, 5 and 10 micrograms/kg, i.v.) increased blood pressure (BP) and reduced heart rate (HR) in conscious rats. In pithed rats, OXY and UK each increased BP to a greater extent than that observed in conscious rats, but HR was not affected. BP increases following sympathetic nerve stimulation in the pithed rats were not affected by OXY but were reduced by UK at 0.1 Hz and 0.3 Hz. HR responses to nerve stimulation in pithed rats were reduced after OXY at all frequencies, but only at 0.1 Hz following UK. EFA, IDA and RAU inhibited the pressor responses of UK, with EFA being most potent. OXY-induced pressor responses were inhibited by all three antagonists, RAU being the least potent. HR responses to either OXY or UK were not affected by the antagonists. Taken together, the data suggest that: 1) alpha 2-adrenoceptors contribute less to the vascular response to OXY than to UK based upon the antagonistic effect of RAU; 2) prejunctional I1 receptors maybe more prevalent in the heart than in vascular tissue based upon the response to OXY in pithed rats. Thus, the heterogeneity among receptors mediating cardiac and vascular responses are complex.

Adrenergic alpha-Agonists↗

PubMed1996

Effects of MaxEPA on salt-induced hypertension: relationship to [3H]nitrobenzylthioinosine binding sites.

We investigated the effects of dietary MaxEPA (a major source of eicosapentaenoic acid in fish oil) supplementation on blood pressure (BP) responses and heart rate (HR) of Dahl salt-sensitive (SS) rats fed low (0.4% NaCl) and high (8.0% NaCl) sodium diets. During a four week treatment period, BP remained normotensive in rats on low salt diet but was significantly elevated in those on high salt diet, causing 50% mortality. MaxEPA diminished the BP elevation and prevented the high salt-induced mortality. HR was not affected by either salt diet alone but was reduced in the presence of MaxEPA. At the end of the treatment period, the distribution of [3H]nitrobenzylthioinosine ([3H]NBMPR) binding, a putative marker of adenosine transport and metabolism, was estimated in selected rat tissues in order to evaluate the role of the purinergic system in the BP lowering effect of MaxEPA. Maximal [3H]NBMPR binding capacity (Bmax) in the kidney and platelets were 39% and 82% lower, respectively, in rats on high salt diet than in those on low salt diet. MaxEPA significantly blunted the decrease in Bmax in the kidney but not in platelets and increased Bmax in heart (48%) of low salt group. There were no changes in dissociation constants (Kd). The results suggest that MaxEPA can attenuate salt-induced hypertension, reduce salt-induced mortality and protect the integrity of kidney NBMPR binding sites in salt-induced hypertension.

Affinity Labels↗