Biomedical subjects

F P Field

Publications and source records attributed to F P Field.

At least 19 recordsLinked to original sources

PubMed1991

Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle.

CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethyolcarboxamidoa denosine) is an adenosine agonist that has been reported recently to bind selectively to adenosine A2 receptors in rat brain. This adenosine agonist, and the parent compound NECA (5'-N-ethylcarboxamidoadenosine), were found to be potent vasorelaxants of prostaglandin F2 alpha (PGF2 alpha) precontracted porcine coronary smooth muscle with EC50s of 4.5 and 9.7 nM, respectively. Schild analysis of the inhibition of CGS 21680, NECA and 2-chloroadenosine induced relaxation of the porcine coronary artery by CGS 15943 (9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-C]quinazolin-5-amine), an A2 receptor antagonist, yielded identical pA2 values for the antagonist (approximately 9.3). This indicates that the same receptor mediates the effects of these three adenosine agonists. NECA and CGS 21680 were equipotent in most vascular preparations except in the canine coronary artery. Porcine coronary arterial rings contracted with PGF2 alpha were relaxed by NECA or CGS 21680 as well as by nitroprusside; those contracted with KCl (40 mM) were relaxed only by nitroprusside. In rabbit aorta, contractions induced by phenylephrine or PGF2 alpha were inhibited by nitroprusside but not by NECA or CGS 21680. Thus, the adenosine A2 receptor agonists, NECA and CGS 21680, are potent vasorelaxants that display regional vascular and species variations that differ from those of nitroprusside.

Adenosine↗

PubMed1989

Histological and biomechanical assessment of articular cartilage from stored osteochondral shell allografts.

Normal and stored articular cartilage from the medial tibial plateaus of mature canine knee joints were evaluated histologically and biomechanically. The medial plateaus from the right knee (control) were assessed fresh, while the left (stored) were preserved in culture media at 4 degrees C for 3, 7, 14, or 28 days and then evaluated. Biomechanically, confined compression tests were performed on all specimens to determine the aggregate modulus and apparent permeability of the articular cartilage. Histologically, Safranin O- and hematoxylin and eosin (H&E)-stained sections were evaluated. All stored cartilage specimens had an aggregate modulus on average lower than normal, but the differences were not significant (p greater than 0.10). The apparent permeability was on average higher than but also not significantly different from normal (p greater than 0.10). Time in storage (up to 28 days) did not have a significant effect on the biomechanical properties of stored cartilage normalized by control values (p greater than 0.50). Safranin O and H&E histological evaluation also showed no overall changes in cell appearance or staining of the stored cartilage when compared with control for the time periods studied.

Animals↗

PubMed1989

Morphological and biomechanical evaluations of neocartilage from the repair of full-thickness articular cartilage defects using rib perichondrium autografts: a long-term study.

Neocartilage regenerated from rib perichondrium autografts implanted into full thickness cartilage defects made in the femoral condyle of rabbit knees were evaluated for periods up to 1 yr. Two postoperative treatment effects were studied, one with ad lib. caged activity (CAGE) and the other with the operated knee placed on a continuous passive motion machine for 2 weeks (8 h day-1 for 5 days week-1) followed by caged activity (PM). Animals were sacrificed at 6, 12, 26 and 52 weeks after surgery. The neocartilage was evaluated histologically and biomechanically and compared with the contralateral unoperated side. Visually, the neocartilage appeared to have an appearance similar to that of surrounding cartilage at 52 weeks, with an excellent degree of confluence with the neighboring tissue. The newly grown tissues were morphologically similar to normal hyaline articular cartilage. The dynamic shear moduli for the neocartilage from both the CAGE and PM groups significantly increased with postoperative healing time (p less than 0.05). However, there was no statistical difference between the two treatment modalities (p greater than 0.10), indicating that the passive motion did not enhance the long-term repair of the cartilage defect. These results support our hypothesis that neocartilage regenerated from perichondrial autograft remains intact over time.

Animals↗

PubMed1988

Correlation between binding affinities for brain A1 and A2 receptors of adenosine agonists and antagonists and their effects on heart rate and coronary vascular tone.

The activities of a series of A1 and A2 adenosine receptor agonists and antagonists were determined using radioligand binding techniques in rat brain tissues. The potencies of these agonists on heart rate and coronary vascular tone were also assessed in the perfused working rat heart preparation. The order of potency of these agonists in producing negative chronotropic effects was similar to the rank order for their A1 receptor binding activities [6-N-cyclohexyladenosine (CHA) = 6-N-(R-phenylisopropyl)-adenosine greater than 5'-N-ethylcarboxamideadenosine (NECA) = 2-chloroadenosine greater than 2-phenylaminoadenosine] with a correlation coefficient of 0.97. Their order of potency in reducing coronary vascular tone followed the same rank order as their A2 receptor binding activities with a correlation coefficient of 0.97 (NECA greater than 2-chloroadenosine = 6-N-(R-phenylisopropyl)-adenosine = 2-phenylaminoadenosine greater than CHA). In addition, the antagonists 8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]ox]phenyl-1,3- dipropylxanthine (XAC), 1,3-dipropyl-8-(2-amino-4-chlorophenyl) xanthine (PACPX) and 8-phenyltheophylline (8-PT) blocked the negative chronotropic effect of CHA and the vasodilatory effect of NECA in a concentration-dependent manner. The same order of potency of the antagonists was noted in blocking CHA-induced bradycardia and A1 receptor binding activities (XAC = PACPX greater than 8-PT). A similar correlation was observed for their effects in blocking NECA-induced vasodilation and A2 receptor binding activity (XAC greater than PACPX greater than 8-PT).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1987

Temperature dependent behavior of the canine medial collateral ligament.

The temperature dependent tensile behavior of ligament was investigated from 2 degrees C to 37 degrees C. Nondestructive cyclic tests were performed on ten canine femur-medial collateral ligament-tibia (FMT) complexes at sequential temperatures of 22 degrees C, 22 degrees C, 27 degrees C, 32 degrees C, 37 degrees C, and again at 22 degrees C. The samples were rested at zero load between tests for sufficient time periods to allow for full recovery from the ligament's time and history dependent viscoelastic properties. Ten additional FMT complexes were sequentially tested in a similar fashion, but at temperatures of 22 degrees C, 22 degrees C, 2 degrees C, 6 degrees C, 14 degrees C, and 22 degrees C. All canine FMT complexes showed temperature dependent viscoelastic properties: the measured area of hysteresis decreased with increasing temperature; the cyclic load relaxation behavior plateaued to a higher value at lower temperatures; and the tensile load at a predetermined ligament substance strain level had an inversely proportional relationship with respect to temperature.

Animals↗

PubMed1987

Sodium pump activity and norepinephrine responsiveness of femoral arterial smooth muscle from DOCA-salt rats.

This study investigated the effect of sodium pump activity on vascular smooth muscle responsiveness to norepinephrine (NE) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Dose-response curves to NE were generated in normal (5.9 mM), high (10 mM) or 0 mM potassium (K) Krebs physiological solution. Inhibition of the sodium pump (0 mM K) in femoral arterial smooth muscle from control rats resulted in an increased response to NE which was similar to the DOCA-salt rat, while increasing sodium pump activity (10 mM K) in femoral arterial smooth muscle from DOCA-salt rats resulted in a decreased response which was similar to controls. These results show that altering sodium pump activity in vitro by changing extracellular K concentration can affect femoral arterial smooth muscle responsiveness to NE in both control and DOCA-salt rats. Alterations in sodium pump activity observed in vascular smooth muscle from DOCA-salt hypertensive rats may contribute to the increased NE responsiveness and increased vascular resistance seen in this model of hypertension.

Animals↗

PubMed1987

Perichondrial autograft for articular cartilage. Shear modulus of neocartilage studied in rabbits.

Perichondrial autografts were used for the repair of large, full-thickness articular cartilage defects in the rabbit medial femoral condyle. The effects of duration of implantation and activity were studied by evaluating the neocartilage mechanically and morphologically. The complex shear moduli for the neocartilage were found to increase during the 26 weeks' observation time. Complete filling of the defect with neocartilaginous tissue was seen in a total of 24 successful experimental samples. It appeared that in the initial 6 weeks passive motion applied intermittently for 2 weeks enhanced the formation of quality neocartilage, i.e., the magnitude of the complex shear moduli was higher than those nontreated. However, these differences disappeared when longer time periods were considered.

Animals↗

PubMed1986

Sodium pump activity and calcium relaxation in vascular smooth muscle of deoxycorticosterone acetate-salt rats.

The Na+-K+ pump activity was determined in femoral arterial smooth muscle from deoxycorticosterone acetate (DOCA)-salt hypertensive rats using potassium relaxation and ouabain-sensitive 86Rb uptake as indices. The membrane-stabilizing effect of calcium and its relation to Na+-K+ pump activity also were examined. Femoral arteries from DOCA-salt rats exhibited a greater relaxation in response to potassium addition after contraction with norepinephrine in a low potassium (0.6 mM) Krebs solution. The concentration of potassium required to produce a 50% relaxation was significantly less in DOCA-salt rats. Ouabain-sensitive 86Rb uptake was significantly greater at 3, 10, and 20 minutes of 86Rb incubation in femoral arteries from DOCA-salt rats. Linear regression analysis revealed a significant correlation between the uptake of 86Rb and time of incubation in both control and DOCA-salt rats. A significant difference in the slopes of the regression lines showed that the rate of uptake was greater in DOCA-salt rats. No difference was observed in ouabain-insensitive 86Rb uptake. A dose-dependent relaxation in response to increasing concentrations of calcium following contraction to norepinephrine was observed in femoral arteries from control and DOCA-salt rats. The relaxation was directly dependent on the level of extracellular potassium and was blocked by ouabain. Femoral arteries from DOCA-salt rats relaxed to a significantly greater extent in response to calcium at each level of potassium when compared with controls. These results provide further evidence for an increase in Na+-K+ pump activity in vascular smooth muscle from DOCA-salt hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Extracellular calcium and altered vascular responsiveness in the deoxycorticosterone acetate-salt rat.

This study investigated the effects of altered extracellular Ca2+ on in vitro femoral arterial smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Compared with controls, femoral arteries from DOCA-salt rats showed a significant increase in sensitivity to KCl and norepinephrine in normal Ca2+ (2.5 mM). Although no difference in maximal contractile response to KCl was observed between groups, there was a significant difference in maximal response to norepinephrine. Dose-response curves in low Ca2+ (0.25 mM) resulted in a significant decrease in the sensitivity of femoral arteries from DOCA-salt rats to KCl and NE so that the responses were similar to those of controls. Relaxation of femoral arteries from DOCA-salt rats after washout of the KCl contraction was significantly slower than that of controls in both low and normal Ca2+. Isoproterenol-induced relaxation of femoral arteries from DOCA-salt rats was significantly attenuated in normal Ca2+. Sensitivity of femoral arteries from DOCA-salt rats to isoproterenol increased in low Ca2+, but maximal relaxation was unaltered. Whereas no difference in maximal relaxation to NaNO2 was seen in femoral arteries from either group in normal Ca2+, a significant decrease in sensitivity to NaNO2 was observed in femoral arteries from DOCA-salt rats. In low Ca2+ the response of femoral arteries from DOCA-salt rats to NaNO2 was similar to that of controls. These results suggest that the increased vascular smooth muscle responsiveness to KCl and norepinephrine seen in DOCA-salt hypertension is due to increased sensitivity of the vascular smooth muscle to Ca2+. Extracellular Ca2+, however, plays only a minor role in the decreased vasodilator responsiveness seen in this form of hypertension.

Animals↗

PubMed1986

Differential effects of phentolamine on the responsiveness of aortic and femoral smooth muscle from normotensive and DOCA/NaCl hypertensive rats.

The in vitro responsiveness of rat aortic and femoral arterial smooth muscle from normotensive and deoxycorticosterone acetate (DOCA)/NaCl-induced hypertensive rats to potassium chloride (KCl) and isoproterenol (ISO) in the presence and absence of the alpha-adrenergic blocker phentolamine was investigated. Femoral but not aortic smooth muscle from the DOCA/NaCl rat exhibited an enhanced sensitivity to KCl stimulation when compared to controls. Phentolamine had no effect on femoral smooth muscle from control or DOCA/NaCl rats. However, a significant decrease in the sensitivity of aortic smooth muscle responsiveness to KCl in the presence of phentolamine was observed in both the control and hypertensive groups. Isoproterenol-induced relaxation of both aortic and femoral smooth muscle was significantly attenuated in the DOCA/NaCl rat when compared to controls. Incubation with phentolamine resulted in a significant increase in the relaxation response to ISO in aortic and femoral smooth muscle from controls. This increased responsiveness, however, was not observed in DOCA/NaCl rats. The contractile response to high doses of ISO was attenuated with phentolamine in all groups. A significant increase in the sensitivity to norepinephrine (NE) was observed in both aortic and femoral smooth muscle from the DOCA/NaCl rat when compared to controls. Whereas aortic and femoral smooth muscle from the DOCA/NaCl rat which had been exposed to phentolamine previously in the experiment exhibited a significant decrease in the sensitivity to NE following a one hour washout of the phentolamine, no long-lasting effect of phentolamine was apparent in vessels from controls. The results of this study confirm previous studies that the vascular smooth muscle responsiveness to NE is increased and ISO-induced relaxation is decreased in the DOCA/NaCl rat and demonstrate that these altered adrenergic responses are similarly manifested in the femoral smooth muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Effects of prenatal exposure to tricyclic antidepressants on adrenergic responses in progeny.

Studies were undertaken to examine the effects on cardiovascular function in progeny of rats treated maternally with the tricyclic antidepressants, doxepin and imipramine. Doxepin was administered once daily during the first trimester (days 1-7), second trimester (days 8-14) or third trimester (days 15-21) of pregnancy, while imipramine was administered during the third trimester only. Exposure to doxepin during the first or second trimester increased infant mortality rate, while third trimester exposure to imipramine, but not doxepin, enhanced infant mortality. Additionally, third trimester imipramine, but not doxepin, exposure reduced birth weight and growth rate of progeny. Tests of cardiac and aortic response to adrenergic stimulation revealed that third trimester exposure to either of these tricyclic antidepressants enhance the responsiveness of the beta-adrenergic system in the aorta, while doxepin exposure during the other trimesters was without effect on aortic beta-response. Prenatal exposure to these antidepressants did not alter blood pressure or the contractile response of aortic tissues to alpha-receptor stimulation. Collectively, these studies reveal that at doses of tricyclic antidepressants which do not cause dysmorphic effects on the fetus, subtle alterations occur in selective adrenergic functions which can persist into adulthood in the rat.

Animals↗

PubMed1984

Effects of NaCl on vascular responsiveness in male rats.

The effect of chronic salt treatment on systolic blood pressure and vascular adrenergic responsiveness was studied in rats. Vascular reactivity of aortic smooth muscle to potassium chloride and sodium nitrite was similar in both groups, indicating that salt treatment did not alter the regular contraction and relaxation process of the smooth muscle. Isoproterenol-induced relaxation was similar for both treated and control groups demonstrating that salt treatment had no effect on vascular beta-adrenergic responsiveness. However, when aortic smooth muscle was incubated with angiotensin II or norepinephrine, a significant increase in responsiveness was observed in the aortic smooth muscle of the salt-treated group compared to the control group. Collectively, these results suggest that salt, per se, does not affect systolic blood pressure or peripheral beta-adrenergic responsiveness, but does result in a significantly enhanced alpha-adrenergic responsiveness. The implication of these results for experimental hypertension are discussed.

Angiotensin II↗

PubMed1984

Time course alterations in vascular adrenergic responsiveness in the DOCA/NaCl-treated rat.

Rats treated with desoxycorticosterone acetate and sodium chloride (DOCA/NaCl) developed a time-dependent increase in blood pressure which was associated with a reduced in vitro beta- and an elevated alpha-adrenergic responsiveness. Isoproterenol-induced relaxation of aortic smooth muscle from the DOCA-NaCl-treated rats was similar to controls 1 week after treatment, was significantly attenuated as the blood pressure began to rise (week 4) and was completely abolished when the blood pressure exceeded 150 mm Hg (week 12). The aortic smooth muscle sensitivity to norepinephrine was significantly increased prior to (week 1), during the rise (week 4) and during the maintenance of an elevated systolic blood pressure (greater than 150 mm Hg; week 12). No significant differences were observed between the two groups in either the contractile response of the aortic ring preparations to potassium chloride or in the relaxation properties in response to sodium nitrite. These results demonstrate that alterations in both the alpha- and beta-adrenergic responsiveness occur in the DOCA/NaCl-treated animal. The enhancement of the alpha-adrenergic responsiveness occurs prior to any change in blood pressure, while the attenuated beta-adrenergic responsiveness parallels the elevation in blood pressure, suggesting that these reciprocal alterations of adrenergic responsiveness may be responsible for the eventual development of hypertension induced with DOCA/NaCl treatment in rats.

Animals↗

PubMed1984

Effect of high blood pressure stress on vascular adrenergic responsiveness in the spontaneously hypertensive rat.

A model in which partial ligation of the left external iliac artery results in a decrease in mean arterial blood pressure to the ipsilateral femoral artery (70 mmHg; protected) while mean pressure increases in the contralateral femoral artery (125 mmHg; unprotected) was used to determine the effect of high blood pressure stress on vascular adrenergic responsiveness. Age-matched (5 week old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in the study. Partial ligation was performed at 6 weeks of age and vascular reactivity studies undertaken at 10 weeks of age when the SHR were considered hypertensive (indirect systolic blood pressure greater than 150 mmHg). Force-tension analysis of femoral arterial rings revealed that all tissues contracted maximally at 1.0 gram of preload force. This value was used in subsequent studies on adrenergic responsiveness. Isoproterenol-induced relaxation was significantly attenuated in rings of vascular smooth muscle from unprotected femoral arteries of the SHR, however, the response of rings from protected arteries of the SHR was similar to that of the protected and unprotected arteries of the WKY animal. Unprotected arteries of the SHR exhibited a greater response to norepinephrine stimulation when compared to protected arteries of the SHR as well as unprotected and protected arteries of the WKY animal. This study suggests that alterations in vascular alpha- and beta-adrenergic responsiveness in the SHR are most probably due to the increase in blood pressure.

Animals↗

PubMed1983

Age-related decline in adrenergic responsiveness of the kidney, heart and aorta of male rats.

Studies were undertaken to evaluate the rate of loss in beta-adrenergic responsiveness in the kidney, heart and thoracic aorta in aging male rats. The dipsogenic response to isoproterenol (15 micrograms/kg B.W.) was reduced by 53 and 78% in middle-aged (12 to 13 months) and old (24 to 25 months) versus young (4 to 5 month) rats. In contrast, the drinking response to angiotensin I was unaltered with increasing age, indicating that the decline in B-response was not due to an alteration in the processing of or response to angiotensin. The chronotropic response of the heart to isoproterenol (5 micrograms/kg B.W.) was only moderately decreased by middle-age but was reduced by 69% in old versus young rats. Similarly, the isoproterenol-induced relaxation of aortic rings, in vitro was unchanged at 12 to 13 months of age but was severely diminished at 24 to 25 months of age. Thus the decline in beta-adrenergic responsiveness which accompanies the aging process appears to occur at different rates in several peripheral tissues. In vitro, aortic rings exhibited an age-related decline in contractile response to increasing dose of potassium chloride (KCL) and norepinephrine (NE). Maximum contractility in response to KCl was reduced by middle-age and declined further by 24 to 25 months of age. Similarly, the contractile response of aortic rings to low doses of NE (5 X 10(-10) and 1 X 10(-9)M) was significantly reduced at both middle and old age. Thus, both alpha-adrenoceptor mediated as well as non-receptor mediated aortic contractility are reduced progressively with increasing post-maturational age.

Age Factors↗

PubMed1983

Changes in vascular responsiveness following chronic exposure to cold in the rat.

The responsiveness of smooth muscle from rings of aortic tissue of cold-acclimated (CA, 6 degrees C, 5-15 wk) rats to both alpha- and beta-adrenergic agonists and KCl was tested and compared with that of warm-adapted (25 degrees C) controls. alpha-Adrenergic stimulation, induced by low doses (10(-8)-10(-7) M) of phenylephrine and norepinephrine in the presence and absence of the beta-adrenergic antagonist, propranolol, resulted in the development of less active tension by aortic smooth muscle from CA rats than from controls. Similar results were observed with the weakly alpha 1-adrenergic agonistic activities of tyramine, clonidine, and high concentrations of isoproterenol (10(-6)-10(-4) M). There was also a significant reduction in the tension developed by smooth muscles of the aortas from CA rats when depolarized with KCl in concentrations ranging from 8 to 20 mM. In contrast, aortic smooth muscle, contracted to 75% of maximum with KCl, showed an enhanced relaxation to the beta-adrenergic agonist, isoproterenol, in CA rats. These studies suggest that acclimation of rats to cold results in both a decrease in alpha-adrenergic responsiveness and an increase in beta-adrenergic responsiveness in vascular smooth muscle as well as a change in the biochemical events that couple activation of adrenergic receptors to changes in vasomotor tone.

Acclimatization↗

PubMed1982

Interrelationships among blood pressure, renal function, thyroid activity and renal thyroid depressing factor in renal hypertensive rats.

Renal hypertension in rats was accompanied by both a decrease in thyroid activity (i.e., decreased total serum triiodothyronine concentration, increased serum thyroid-stimulating hormone concentration and increased thyroid weight) and renal function (i.e., reduced renal concentrating ability, increased blood urea nitrogen and serum creatinine concentrations). Systolic blood pressure, thyroid activity and level of renal function of individual hypertensive rats correlated significantly with the content of a thyroid-depressing factor in their kidneys. The results suggest, but do not prove, that a factor released by the kidneys during elevation of blood pressure and/or reduction in renal function may reduce thyroid function in the rat.

Animals↗

PubMed1981

Use of lactoperoxidase-catalyzed iodination of L-tyrosine to assess antithyroid activity of a factor present in certain tissues of mammals.

A factor, present in the kidneys of rats, has been shown to inhibit thyroid activity both in vivo (rat) and in vitro (porcine and bovine thyroid slices). The aim of the present study was to quantitate the inhibitory activity of this factor in renal and other tissues from rats by means of the lactoperoxidase-catalyzed iodination of L-tyrosine. Supernatants of renal homogenates (10,000, 27,000 and 35,000 g) obtained from rats inhibited this in vitro iodination system as well as the lactoperoxidase-catalyzed oxidation of guaiacol. The 35,000-g supernatant from both renal and hepatic tissues contained the greatest inhibitory activity per milligram of protein. Supernatants of homogenates (35,000-g fraction) from testes contained one eighth to one third the activities of liver and kidney, respectively. Kidneys of other species including fetal goat, mature goat, fetal lamb, mature monkey and mature dog, were also shown to contain the thyroid-depressing factor. These studies suggest that the thyroid-depressing factor is found mainly in liver and kidneys of the rat and that it is not unique to the rat but is present in the kidneys of other species as well.

Animals↗