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Biomedical subjects

M J Fregly

Publications and source records attributed to M J Fregly.

248 records · Page 14Linked to original sources
PubMedDate not supplied

Renal-thyroid interrelationship in normotensive and hypertensive rats.

An increase in the weight of the thyroid gland, accompanied by reductions in uptake and release of 1311, serum T3 and reverse T3 concentrations and an increase in serum TSH concentration, occurs during the development of renal hypertension in rats. Renal function, as assessed by BUN, serum and urinary creatinine concentrations, and ability to concentrate urine during dehydration, is depressed. The kidneys of both normotensive and renal hypertensive rats contain a thyroid depressing factor (TDF) which inhibits uptake of 131I both in vivo and in vitro as well as inhibiting the lactoperoxidase enzyme in vitro. The kidneys of renal hypertensive rats contain less, and the serum more, TDF than those of normotensive rats. Whether TDF is produced as a result of hypertension per se or as a result of renal damage accompanying hypertension remains for further study. TDF appears to be a peptide with a molecular weight in the range of 400 to 419 daltons.

Animals↗
PubMedDate not supplied

Factors affecting angiotensin II-induced hypothermia in rats.

Systemic administration of angiotensin II (AII) to the rat has previously been shown to induce a dose-dependent, hypothermic response manifested by a fall in colonic temperature (CT), a decrease in heat production and an increase in tail skin temperature (TST). The factors mediating AII-induced hypothermia and their site of action were the subjects of the present investigation. To this end, intracerebroventricular administration of 1 microgram of AII induced a 0.4 degrees C reduction in CT and a 2.4 degrees C increase in TST. In contrast, SC administration of 200 micrograms angiotensin III/kg induced a slight increase in CT but had no affect on TST. Pretreatment with the AII-receptor antagonist, saralasin, at either 1 or 10 micrograms/kg, SC did not affect either the fall in CT or the increase in TST induced by administration of 200 micrograms AII/kg, SC. However, the administration of 100 micrograms saralasin/kg, SC attenuated both the fall in CT and the increase in TST induced by either 100 or 200 micrograms AII/kg. Since both the presynaptic alpha adrenoceptor agonist, clonidine, and the opioid antagonist, naloxone, modulate the pressor and dipsogenic responses to AII, their effects on AII-induced hypothermia were tested. Both clonidine (25 micrograms/kg, SC) and naloxone (1 mg/kg, IP) enhanced the fall in CT. Clonidine lengthened the duration of the increase in TST while naloxone had no effect. Pretreatment with the presynaptic adrenoceptor antagonist, yohimbine (300 micrograms/kg, SC), did not alter the hypothermic response to administration of AII. To determine whether vasodilation of the tail of the rat was mediated by AII-induced prostaglandin release, indomethacin (4 and 6 mg/kg) was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMedDate not supplied

Dipsogenic effect of L-5-hydroxytryptophan in rats.

The precursor of serotonin, l-hydroxytryptophan (5HTP), is a potent dipsogen in the rat. Peripheral administration of increasing doses of this compound increased water intake in a dose-dependent fashion. Peripheral administration of other analogs of tryptophan, including d-tryptophan, l-tryptophan and acetyltryptophan, failed to affect water intake at a dose at which 5HTP induced maximal drinking (25 mg/kg, SC). The dipsogenic effect of melatonin, one of the metabolites of serotonin, was also tested. At any of 6 different doses (0.5 to 50 mg/kg, SC), melatonin failed to affect water intake in the rat. The mechanism by which 5HTP induces drinking is not known with certainty but could involve its conversion to serotonin, a known dipsogenic agent.

5-Hydroxytryptophan↗
PubMedDate not supplied

Effect of nonpeptide angiotensin receptor antagonists on water intake and salt appetite in rats.

Nonpeptide angiotensin AT-1 and AT-2 receptor antagonists were administered cerebroventricularly to rats and their effects on various types of angiotensin II (AII)-stimulated water and NaCl intakes examined. The AT-1 receptor blocker, losartan potassium (DUP 753), inhibited water intake evoked by central administration of AII, with the 50% inhibitory dose being less than 0.1 microgram. The functional inhibition by higher doses lasted at least 1 h. The AT-2 receptor antagonist PD 123319 also inhibited AII-induced water intake, but at doses about tenfold higher than losartan. Central, but not peripheral, administration of losartan partially inhibited NaCl intake induced by either sodium depletion, treatment with angiotensin converting enzyme inhibitors (CEIs), or adrenalectomy. PD 123319 partially inhibited NaCl intake induced by both sodium depletion and administration of CEI, but not after adrenalectomy. Another AT-2 receptor antagonist, CGP 42112A, likewise inhibited NaCl intake after sodium deprivation. These data suggest that both AT-1 and AT-2 receptor subtypes in the brain are involved in angiotensin-related water and NaCl intakes.

Adrenalectomy↗
PubMedDate not supplied

Body fluid distribution in rats with cold-induced hypertension.

The purpose of this experiment was to determine body fluid distribution during chronic cold exposure and to further understand the mechanism of cold-induced hypertension. Blood pressures, hematocrit, and the plasma, blood, and extracellular fluid volumes were measured in rats at intervals of 1, 3, and 5 weeks after exposure to cold (5 degrees C). Resting systolic, diastolic, and mean blood pressures measured by direct arterial cannula were significantly elevated in a time-dependent manner over the duration of cold exposure. The increase in diastolic blood pressure, which reflects the peripheral vascular resistance, exceeded that of systolic blood pressure after both 3 and 5 weeks of exposure to cold. Pulse pressure was significantly decreased by 3 and 5 weeks of cold exposure. The plasma, blood, and extracellular fluid volumes were significantly increased after both 1 and 3 weeks of exposure to cold, but had returned to control levels by 5 weeks of cold exposure. Cold exposure, however, did not affect the hematocrit. The 2-h water intake after the cold-exposed rats were returned to warm (25 degrees C) (thermogenic drinking) was significantly increased compared to that of warm-acclimated rats during the first, third, and fifth week of exposure to cold. The present results suggest that the development of cold-induced hypertension is associated with blood volume expansion, and that the elevated blood pressure is maintained by increased peripheral vascular resistance without blood volume expansion. The results also imply that exposure to cold induces a dehydration in rats.

Acclimatization↗
PubMedDate not supplied

Effect of cycloheximide on temperature regulation in rats.

The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.

Animals↗
PubMedDate not supplied

Dependence of beta-adrenergic responsiveness on thyroid state of male rats.

The dose of thyroxine (0-150 micrograms/kg body weight) administered subcutaneously daily to surgically thyroidectomized male rats was correlated significantly with their metabolic activity as assessed by rate of oxygen consumption and colonic temperature. There was a significant dose-dependent increase in total serum thyroxine, triiodothyronine and reverse-triiodothyronine concentrations with increasing doses of thyroxine administered. The cardiostimulatory response to administration of isoprenaline (8 micrograms/kg body weight s.c.) was also correlated directly with the dose of thyroxine administered. The concentration of cardiac beta-adrenoceptors in these animals was correlated significantly with total serum thyroxine and triiodothyronine concentrations, basal heart rate, and the chronotropic response to administration of isoprenaline.

Animals↗
PubMedDate not supplied

Prevention of DOCA-induced hypertension in rats by chronic treatment with tryptophan.

Hypertension developed within 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA, 30 mg/kg, s.c., weekly) and given isotonic saline to drink. Chronic dietary administration of tryptophan (50 g/kg food) reduced intake of saline solution and prevented the elevation of systolic blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24 h dehydration that is characteristic of DOCA-treated rats. Other tests were carried out to assess the responsiveness to the beta-adrenergic agonist, isoproterenol. The tests included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking response of DOCA-treated rats to acute administration of isoproterenol was returned to that of untreated controls by chronic treatment with tryptophan. However, the reduced chronotropic response of the heart of DOCA-treated rats to administration of isoproterenol was unaffected. The cardiac hypertrophy characteristic of DOCA-treatment was attenuated significantly by chronic treatment with tryptophan. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, and cardiac hypertrophy in rats. The mechanism by which tryptophan protects is unknown and requires additional study.

Animals↗
PubMedDate not supplied

Effect of in vitro administration of captopril on vascular reactivity of rat aorta.

The effect of acute administration of captopril, an angiotensin converting enzyme inhibitor, on vascular responses of rings of rat aortic smooth muscle was tested in vitro. Dose-response curves for various vasoactive agents were obtained before and after exposure to captopril (2 x 10(-4) M) for 30 minutes. In the presence of captopril, contractile responses to angiotensin I (5 x 10(-10) to 5 x 10(-8) M) were attenuated significantly, probably as a result of decreased local conversion of angiotensin I to angiotensin II. Contractile responses to angiotensin II (10(-11) to 5 x 10(-9) M) were not affected by captopril. All responses to norepinephrine (10(-9) to 10(-4) M) and phenylephrine (10(-8) to 10(-4) M) were attenuated significantly from control in the presence of captopril. In the presence of the alpha-adrenergic antagonist, phentolamine, captopril did not affect either the contractile responses to KCl (30 to 100 mM) or the isoproterenol-induced (10(-8) to 10(-5) M) relaxation of KCl-depolarized tissue. These results suggest that captopril decreased vascular responsiveness to alpha-adrenergic agonists but not to beta-adrenergic agonists. Low concentrations of bradykinin (10(-10) to 10(-8) M) induced contraction in KCl-depolarized tissue while higher concentrations (10(-7) and 10(-6) M) induced relaxation. In the presence of captopril, relaxation occurred at all concentrations of bradykinin (10(-10) to 10(-6) M), probably as a result of decreased degradation of the bradykinin. These data suggest depression of alpha-adrenergic responsiveness in vascular smooth muscle as another potential antihypertensive action of captopril.

Angiotensin I↗