Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

At least 37 records · Page 2Linked to original sources

PubMed1995

Effect of administration of angiotensin II and isoproterenol, alone and in combination, on drinking and tail skin temperature of the rat.

Both angiotensin II (AII) and the beta-adrenergic agonist isoproterenol are well known to induce drinking and increase tail skin temperature (TSK) in rats. Previous studies have shown that these two compounds have an additive, rather than interactive, dipsogenic effect when administered together. The present studies confirmed the additivity of the dipsogenic effect of the two compounds and attempted to extend these results to TSK. The results reveal that at a series of dosage combinations of AII [100 and 125 micrograms/kg, subcutaneously (SC)] and isoproterenol (ISOP) (10, 12.5, and 25 micrograms/kg, SC) administered together, the increase in TSK usually induced by each compound was canceled. This occurred at the lower doses of ISOP in combination with AII. Thus, the differences between dipsogenic and thermoregulatory effects of combined doses of AII and ISOP suggest a difference in central integration. Important differences between the thermoregulatory responses to administration of the two compounds include increases in metabolic rate and colonic temperature when ISOP is administered and decreases in both when AII is administered. It is suggested that the effect of the two compounds to cancel each other with respect to TSK is related to their opposite effects on metabolic rate.

Angiotensin II↗

PubMed1995

Effect of renal denervation on elevation of blood pressure in cold-exposed rats.

The objective of this experiment was to determine whether bilateral renal denervation (RD) prevents the elevation of blood pressure and cardiac hypertrophy characteristically induced by chronic exposure to cold. Four groups (nine male rats each) were used. The kidneys of two groups were bilaterally denervated, while the remaining two groups were sham operated. Systolic blood pressures of the four groups, measured indirectly from the tail, did not differ significantly during the control period and following RD. At this time, 1 RD and 1 sham-operated group was exposed to cold (5 degrees C, 41 degrees F). The remaining RD and sham-operated groups were kept at 25 degrees C. Blood pressure of the cold-exposed, sham-operated group increased significantly during the 1st week of cold exposure (125 +/- 2 mmHg; 1 mmHg = 133.3 Pa), and rose to 139 +/- 4 mmHg by the 5th week, whereas the blood pressure of the RD group exposed to cold remained at the control level (116 +/- 2 mmHg). Both RD and sham-operated cold-exposed groups developed cardiac hypertrophy with significantly increased resting heart rates compared with controls kept at 25 degrees C. Plasma renin activities and renal norepinephrine content of kidneys of both RD groups at 7 weeks after RD were significantly less than those of sham-operated controls, confirming that renal nerves had been severed. Thus, RD prevented the elevation of blood pressure induced by chronic exposure to cold but had no significant effect on cardiac hypertrophy.

Animals↗

PubMed1995

Effect of pyridoxine and tryptophan, alone and combined, on the development of deoxycorticosterone acetate-induced hypertension in rats.

Chronic dietary administration of pyridoxine HCl (300 mg/kg/day), L-tryptophan (1.26 g/kg/day), or a combination of the two can attenuate the elevation of systolic blood pressure in DOCA-salt-treated rats. With these treatments, the characteristic increase in the weight of the heart accompanying chronic administration of DOCA (786 micrograms/kg/day) was also attenuated. Thus, both tryptophan and pyridoxine possess antihypertensive properties, and the combination of the two appeared to provide greater protection than either alone. The results are consistent with the possibility that pyridoxine, an important cofactor in the metabolic pathways for tryptophan, may facilitate the conversion of tryptophan to antihypertensive compounds. Additional studies will be required to determine which of the metabolites of tryptophan possess antihypertensive properties. Pyridoxal phosphate, one of the metabolites of pyridoxine, was also administered chronically in the diet (1.0 and 2.0% by weight) to rats whose blood pressures were elevated by administration of DOCA. The results of this study suggest that pyridoxal phosphate can also lower the blood pressure of rats with established hypertension. Thus, these studies reveal that pyridoxine, pyridoxal phosphate and tryptophan are potential antihypertensive agents.

Analysis of Variance↗

PubMed1995

Increased dipsogenic responsiveness to angiotensin II in rats exposed to cold: rate of loss after return to thermoneutral ambient temperature.

Subcutaneous administration of angiotensin II (Ang II) to rats exposed chronically to 5 degrees C induced an increased drinking response compared with that of warm-acclimated controls. The exaggerated drinking response was also observed when graded doses of Ang II were administered into the lateral cerebroventricle (icv) of chronically cold-exposed rats. A maximal drinking response occurred in cold-treated, but not in control, rats when the lowest dose of Ang II (1.6 ng/rat) was administered icv. Thus, it is clear that the dipsogenic responsiveness to either centrally or peripherally administered Ang II is increased by chronic exposure to cold. To assess whether the increased responsiveness was retained after removal from cold, graded doses of Ang II were administered to rats removed from cold to a thermoneutral environment. The results again showed a maximal responsiveness to the lowest dose of Ang II administered (25 micrograms/kg, sc) to cold-treated rats that had either just been removed from cold or removed from cold 2 hr prior to treatment. Cold-exposed rats had an ED50 for Ang II-induced drinking that was about half that of their warm-acclimated controls. To assess how long the cold-induced increase in dipsogenic responsiveness to Ang II lasted after return to a thermoneutral temperature, rats were removed from cold for 24, 48, or 60 hr and then administered graded doses of Ang II (25, 50, or 100 micrograms/kg, sc). The results suggest that between 46 and 52 hr after removal from cold, the cold-induced increase in dipsogenic responsiveness to Ang II returned to the level of the controls. Hence, the physiological changes in the dipsogenic mechanism induced by exposure to cold are not immediately reversible when the rats are returned to a thermoneutral ambient temperature.

Angiotensin II↗

PubMed1994

Involvement of angiotensin in water intake induced by peripheral administration of a serotonin agonist, 5-carboxyamidotryptamine.

Rats were given peripheral injections of a 5HT1 agonist, 5-carboxy-amidotryptamine (5-CT), and various behavioral, physiological, and neuronal outcomes were documented. 5-CT caused short latency water intake. In rats with a choice between water and hypertonic NaCl, about half of the rats drank only water while the other half showed an initial robust intake of NaCl. Blood pressure was reduced and plasma renin activity increased following 5-CT. The effective half life was 1-3 h, with water intake inhibiting further consumption. Fos-like immunoreactivity (FLI) was induced by 5-CT in regions of the brain identical to those previously shown to be activated by peripheral administration of angiotensin (Ang) II. The role of endogenously-generated Ang II in the dipsogenic action of 5-CT was suggested because captopril inhibited the water intake. Possible mechanisms of 5-CT and Ang II-induced thirst are reviewed, including roles of hypotension and the vagus nerve.

Analysis of Variance↗

PubMed1994

Action of angiotensin converting enzyme inhibitors in rat brain: interaction with isoproterenol assessed by Fos immunocytochemistry.

Low and high doses of angiotensin converting enzyme (ACE) inhibitors have been shown either to enhance or suppress, respectively, the water intake of rats induced by acute administration of isoproterenol. In order to assess the role and sites of action of angiotensin II (Ang II) in this dual action of ACE inhibitors, rats were administered either low or high doses of enalapril or captopril, followed by isoproterenol, and were sacrificed 1 h later for determination of Fos-like immunoreactivity (FLI) in brain. Isoproterenol induced strong FLI in the magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, and moderate staining along the structures of the rostral wall of the lamina terminalis (LT). Low doses of ACE inhibitors either had no effect or slightly increased FLI along the LT following isoproterenol. Enalapril reduced FLI in some other regions, including the parvocellular PVN. In contrast, high doses of ACE inhibitors abolished FLI along the LT, and reduced FLI in the PVN and SON. Captopril, but not enalapril, induced some FLI in the LT, SON and PVN. The data are discussed in terms of access of ACE inhibitors to the brain, and interactions with structures involved in Ang-related water intake.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

Localization of changes in immediate early genes in brain in relation to hydromineral balance: intravenous angiotensin II.

Immediate early genes, detected by Fos- and Jun-like immunoreactivity (FLI, JLI), were induced in discrete regions of the rat brain by intravenous infusion of angiotensin II (Ang II) at dipsogenic doses. The regions included subfornical organ (SFO), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO), supraoptic nucleus (SON), and the magnocellular part of the paraventricular hypothalamus (PVH). These responses were sustained for up to 6 h of infusion. In SFO, FLI was induced preferentially in the posterior part, while JLI occurred in more central regions. Cerebroventricular (ICV) injection of the Ang II type 1 receptor (AT-1) antagonist, losartan potassium, completely prevented the FLI induced by Ang II in these brain regions. ICV injection of the Ang II type 2 receptor (AT-2) antagonist, PD 123319, did not reduce Ang II-induced FLI in SFO, OVLT and MnPO, but markedly attenuated the activation in SON and PVH. To determine whether SFO is the primary site for transduction of the circulating Ang II signal, electrolytic lesions were made in or rostral to the SFO. Rats with complete lesions showed a complete absence of Ang-induced FLI in SON and PVH. The data are discussed in terms of functional mapping of the brain regions activated by circulating Ang II and neural circuitry for water intake, including the possible role of AT-2 receptors in PVH and SON.

Angiotensin II↗

PubMed1994

A role for thyroid hormones in cold-induced elevation of blood pressure and cardiac hypertrophy.

The systolic blood pressures of two groups of rats that were exposed to cold (5 degrees C) for 4 weeks were elevated significantly above that of warm-acclimated controls maintained at 24 degrees C. At this time these groups were given the antithyroid drug aminotriazole in their food at 0.3 g/kg. At the same time, one group was given 15.8 micrograms thyroxine (T4)/kg body mass per day, while the second received 31.6. The doses were chosen as replacement (15.8 micrograms/kg) and twice replacement (31.8 micrograms/kg) for the rats. The results of the study revealed that both groups receiving aminotriazole and T4 had reductions in blood pressure within 1 week of initiation of treatment. Blood pressures reached control level after 5 weeks. Cardiac hypertrophy accompanying cold-induced hypertension was reduced with the lower dose of T4 and prevented with the higher dose. Serum concentrations of T4 and triiodothyronine (T3) in the two treated groups were reduced, while serum thyroid-stimulating hormone concentration and thyroid mass were increased above that of the warm-acclimated control group. This suggests that the rats were hypothyroid relative to the warm-acclimated control group. However, the treated rats grew at the same rate as nontreated, cold-exposed controls and had similar food and water intakes, a similar dipsogenic response to acute administration of isoproterenol, and similar colonic temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗

PubMed1994

Effect of chronic treatment with prazosin and L-arginine on the elevation of blood pressure during cold exposure.

Chronic exposure to cold (5 degrees C) is well known to increase both tyrosine hydroxylase (TH) activity in brown adipose tissue and systemic blood pressure. The effect of chronic dietary administration of the alpha-adrenergic antagonist, prazosin, and the amino acid, L-arginine, on both the elevation of blood pressure during exposure to cold and on TH activity and expression of TH mRNA in the adrenal glands of rats was studied. As observed previously, chronic exposure to cold increased systolic blood pressure significantly and induced cardiac hypertrophy. Chronic dietary treatment with prazosin (8 mg/kg food) and arginine (20 g/kg food) returned blood pressure to control levels, did not affect body weight significantly, but failed to prevent cardiac hypertrophy. Both prazosin and L-arginine reduced the drinking response to administration of angiotensin II. Treatment with arginine and prazosin was accompanied by a significant increase in the urinary outputs of dopamine and L-DOPA. The 3 cold-treated groups (control, L-arginine and prazosin) had increases in plasma T3 and decreases in plasma T4 and plasma renin activity. Plasma concentrations of epinephrine and norepinephrine were increased significantly in the L-arginine-treated group. TH mRNA and TH activity in the adrenal glands were increased in the 3 cold-treated groups and these measures were correlated directly and significantly with plasma norepinephrine and epinephrine concentrations. Although both prazosin and arginine prevented the cold-induced elevation of blood pressure, they did not prevent the increase in TH mRNA, TH activity or epinephrine in plasma. The protective effect of arginine and prazosin in cold-induced hypertension may be related both to their reduction in plasma renin activity and to a reduced responsiveness to angiotensin II, as well as to their abilities to increase the secretion of dopamine.

Adrenal Glands↗

PubMed1994

Direct blood pressure measurements in rats during abrupt exposure to, and removal from, cold air.

When male rats, each bearing an indwelling femoral arterial cannula, were exposed abruptly to cold (5 degrees C), systolic, diastolic, and mean blood pressures increased within 1 hr to levels significantly above those measured prior to exposure to cold. Blood pressures reached maximal levels within 2 hr of exposure to cold and remained elevated during the next seven days. Heart rates, measured at the same time, responded similarly. When cannulated rats that had been exposed to cold for four weeks were removed abruptly to 26 degrees C, systolic, diastolic, and mean blood pressures decreased nearly linearly for 5 hr. By two days after removal from cold, blood pressures stabilized at levels that were still elevated above those observed prior to exposure to cold. In contrast, heart rate returned to precold exposure level by the 13th day after removal from cold. The mechanisms responsible for the elevation of blood pressure during abrupt exposure of rats to cold and the decrease in blood pressure after removal from cold remain to be elucidated.

Animals↗

PubMed1993

Effect of nonpeptide angiotensin AT-1 and AT-2 antagonists on isoproterenol-induced renin release.

The AT-1 receptor antagonist, losartan potassium, produced a large rise in plasma renin activity (PRA) after peripheral, but not intracerebroventricular (ICV), administration. Peripheral, but not ICV administration of losartan also augmented the release of renin induced by peripheral administration of the beta-adrenergic agonist, isoproterenol. The increase in PRA induced by losartan plus isoproterenol was greater than the sum of the increases in PRA induced by the individual treatments. There was, however, no significant enhancement of the hypotensive action of isoproterenol by peripherally administered losartan. The AT-2 receptor antagonist, PD 123319, produced no increase in PRA after either peripheral or ICV injection. However, peripheral injection of PD 123319 slightly increased PRA after peripheral administration of isoproterenol. The data are discussed in terms of the relationship between renin-angiotensin systems and fluid intake, with special reference to the failure of peripherally administered losartan to block isoproterenol-induced water intake.

Angiotensin I↗

PubMed1993

Induction of hyperhydration in rats by IP loading with graded concentrations of NaCl solution.

IP loads of NaCl solution (1% of body weight) varying in concentration from 0.15-1.0 M were used to assess their ability to induce hyperhydration in rats that were allowed access to water for 6 h after loading. The hypertonic concentrations (0.25, 0.50, and 1.0 M) increased water intake in a concentration-related fashion. Only loads of 0.50 and 1.0 M NaCl solution increased urine output above that of water-loaded controls. All hypertonic concentrations increased fluid exchange (i.e., water intake less urine output) significantly. There was a direct concentration-related increase in accumulative mean fluid exchange (delta FE, fluid exchange of NaCl-loaded group less that of control group). There was also a direct concentration-related increase in the time of hyperhydration. When related to each other, delta FE was a direct linear function of time of hyperhydration. The slope and intercept of this relationship were compared with those found in an earlier study for angiotensin II (AngII) and isoproterenol (ISO), both potent dipsogens. Comparison revealed that slopes, but not intercepts, of the relationship between delta FE and time of hyperhydration for any two of the three treatments differed significantly. These data suggest that a given time of hyperhydration can be achieved at a lower delta FE with NaCl loads than with administration of either AngII or ISO. This suggests, in turn, that loading with NaCl solutions produces a more effective hyperhydration than is achieved with administration of either AngII or ISO.

Angiotensin II↗

PubMed1993

Brain angiotensin AT-2 receptor antagonism and water intake.

Intracerebroventricular administration of the angiotensin AT-2 receptor antagonist, PD 123319, inhibited drinking induced in rats by hypertonic NaCl, carbachol, isoproterenol, hypovolemia, and water deprivation, but had no effect on food intake. In contrast, the AT-1 antagonist, losartan potassium, had no effect on these intakes. A model of thirst is presented that incorporates an AT-2 receptor in a final common pathway for drinking.

Angiotensin Receptor Antagonists↗

PubMed1993

Effect of chronic treatment with losartan potassium (DuP 753) on the elevation of blood pressure during chronic exposure of rats to cold.

Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5 degrees C) for 1-3 weeks. The renin-angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II1 receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25 degrees C while the remaining three groups were exposed to cold (5 degrees C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Effect of chronic exposure to cold on vascular responsiveness to phenylephrine and angiotensin II.

Chronic exposure of rats to cold (5 degrees C, 3-4 weeks) results in the development of hypertension. To assess potential mechanisms by which this may occur, the vascular responsiveness to administration of phenylephrine (an alpha-adrenergic agonist) and angiotensin II (AII) was studied in unanesthetized rats at 1, 3 and 5 weeks of exposure to cold (5 degrees C). Vascular responsiveness to intravenous administration of graded doses of phenylephrine was reduced in cold-treated rats, the earliest effect being observed within 1 week of exposure. With respect to AII, vascular responsiveness to graded intravenous doses increased maximally within 1 week of exposure to cold and returned toward the level of the control group at 3 weeks. After 5 weeks of exposure to cold, it had returned to the level of the control group. These results suggest that vascular responsiveness to alpha-adrenergic stimulation appears to be directed toward prevention of an elevation of blood pressure in cold-treated rats. In contrast, vascular responsiveness to administration of AII is increased during the first 3 weeks of exposure to cold, at a time when plasma renin activity is also increased, and may thus play an important role in the initiation of cold-induced elevation of blood pressure.

Angiotensin II↗

PubMed1993

Role of angiotensin II receptors in tail skin temperature response to isoproterenol.

The objective of these experiments was to assess the possibility that the increase in tail skin temperature (TSK) accompanying administration of the beta-adrenergic agonist isoproterenol (ISO) was mediated by angiotensin II (AngII) as a result of stimulation of renin release by ISO. Although AngII is known to be a potent vasoconstrictor in mammals, acute administration of this peptide to rats induces a vasodilation of blood vessels in the tail and an increase in TSK. The objective was approached in several (DuP 753); ways: (i) use of the nonpeptide AngII receptor antagonist losartan potassium (DuP 753); (ii) use of the peptide AngII receptor antagonist saralasin; (iii) use of the AngI-converting enzyme inhibitor captopril, and (iv) chronic administration of AngII. The rationale for these experiments was that blockade of AngII receptors (Experiments 1 and 2), inhibition of the enzyme that converts AngI to AngII (Experiment 3), or down-regulation of the AngII receptors (Experiment 4) would be expected to prevent any contribution to the ISO-induced increase in TSK by AngII. The results of these experiments are consistent in revealing that the response of TSK to ISO administration is due in part (approximately 55%) to a direct effect of ISO and in part (approximately 45%) to an indirect effect resulting from the ISO-stimulated release of renin from the kidneys and the formation of AngII in the blood.

Angiotensin II↗

PubMed1992

Marathon running: physiological and chemical changes accompanying late-race functional deterioration.

Twenty-one experienced runners were studied before, during and immediately after a marathon race to ascertain whether either depletion of energy substrate or rise in body temperature, or both, contribute to late-race slowing of running pace. Seven runners drank a glucose/electrolyte (GE) solution ad libitum (Na+ 21 mmol l-1, K+ 2.5 mmol l-1, Cl- 17 mmol l-1, PO4(2-) 6 mmol l-1, glucose 28 mmol l-1) throughout the race; 6 drank water and 8 drank the GE solution diluted 1:1 with water. Although average running speeds for the three groups were not significantly different during the first two-thirds (29 km) of the race, rectal temperature was significantly higher (P < 0.05) and reduction of plasma volume was greater (P < 0.05) in runners who replaced sweat losses with water. During the last one-third of the race, the average running pace of the water-replacement group slowed by 37.2%; the pace slowed by 27.9% in the 8 runners who replaced their sweat loss with GE diluted 1:1 with water (1/2 GE) and 18.2% in runners who replaced fluid loss with full-strength solution (GE). Eleven runners (5 in the water group, 4 in the 1/2 GE group and 2 in the GE group) lapsed into a walk/run/walk pace during the last 6 miles of the race. Ten of these had a rectal temperature of 39 degrees C or greater after 29 km of running, and plasma volume in these runners was reduced by more than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Effect of chronic administration of dexfenfluramine on blood pressure in salt-sensitive rats.

Chronic administration of dexfenfluramine, at a relatively low daily dose, slowed the development of salt-induced elevation of blood pressure in salt-sensitive (Dahl DS and Rapp SS) rats. This effect could not be accounted for by drug-related anorexia alone. Elevated serotonin activity, possibly in the brain, may underlie this antihypertensive action of dexfenfluramine.

Animals↗