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M F Villamil

Publications and source records attributed to M F Villamil.

At least 19 recordsLinked to original sources
PubMed1990

Direct vascular effects in the rat of the vehicles used for the intravenous and oral administration of cyclosporin A.

1. The contraction and relaxation responses to the polyoxyethylated vehicles currently used for the intravenous and oral administration of cyclosporin A in allograft recipients were studied in isolated rat aorta. The results were compared with those obtained with commercially available cyclosporin A for intravenous administration. 2. None of these compounds affected resting tension, noradrenaline-induced contraction or endothelium-independent relaxation produced by sodium nitroprusside or bumetanide. However, they all reversed the relaxation induced by acetylcholine, carbamylcholine or adenosine 5'-triphosphate, by a factor of approximately 66%. 3. This reversal of relaxation was unaffected by indomethacin and did not require the presence of cyclosporin A in the vehicles, and was completely abolished by L-arginine (3 x 10(-5) mol/l). 4. It is concluded that vehicles used for commercial preparations of cyclosporin A interfere with the synthesis of endothelium-derived relaxing factor at an early stage during which L-arginine is made available for enzymatic degradation.

Administration, Oral↗
PubMed1990

Improved method for estimating Ca uptake in vascular smooth muscle using compartmental analysis.

A comparative study on the modeling aspects of Ca uptake in vascular smooth muscle is presented with particular emphasis on determination of the influx rate and its standard error for one- and two-compartment models. Experimental data from our laboratory of 45Ca uptake by dog carotid arteries were optimally fitted to a one-compartment model and were used to compare different estimation methods and experiment designs. Reparameterization of the model equation yielded an expression that allows direct estimation of the influx rate and its standard error. Experiment design with replicated sampling at three to four times were found to provide the highest estimation precision and successful comparisons of influx rates under treatment and control conditions. Two-compartment model data reported in the literature for Ca uptake by cells were reprocessed, yielding standard errors for the rate constant of the fast component an order of magnitude larger than the mean estimate. For this case, a three-parameter variant of the one-compartment model was developed that described the data with acceptable standard errors. Overall we found that the choice of the model that fitted Ca uptake data best required consideration of parameter estimate precision comparisons in addition to F tests of significance between alternate models.

Animals↗
PubMed1989

Vascular relaxing effects of bumetanide.

Bumetanide reduced basal tension of resting carotid arteries as well as tonic contraction elicited by 36 mM of KCl, KNO3 and 0.1 mM norepinephrine but had little effect on phasic response to norepinephrine and angiotensin II. Bumetanide was much more active against norepinephrine than KCl, KNO3 and its effect was not reduced by propranolol. These findings establish a distinction between bumetanide and the Ca antagonists, which do not affect basal tension but selectively inhibit potassium (K+) contracture. On the contrary, this compound resembles the nitrocompounds in that vascular relaxation does not require the integrity of endothelium but is abolished by methylene blue. These two common traits support the view that the increased synthesis of cyclic GMP secondary to guanylate cyclase activation may be directly involved in the vasodilating properties of the drug.

Angiotensin II↗
PubMed1986

Effect of bumetanide on potassium transport and ionic composition of the arterial wall.

Bumetanide (B) (1 mM) decreased K content of dog carotid arteries (Ka) by 11-15%, K turnover (lambda 2) by 31%, and steady-state K fluxes (JK) by approximately 48%. The drug also reduced intracellular (ic) Cl, H2O, and occasionally ic Na. The half-maximal inhibitory concentration of B on JK was close to 40 microM. However, 10 microM still fully reduced ic K, Cl, and H2O but not ic Na. Replacement of external Cl by sulfate or nitrate mimicked the B effects on JK and reduced its capacity of inhibition by approximately 40 and approximately 80%, respectively. Replacement of Na by choline decreased Ka and JK by 90 and 96%, respectively, and rendered B totally ineffective. B also decreased Cl uptake and content of cultured vascular smooth muscle and ic Cl and H2O of whole arteries. Ouabain (Ou) (1 mM) decreased Ka 90%, accelerated lambda 2 four- to fivefold, and reduced JK 45%. Addition of B or removal of external Na or Cl in the presence of Ou returned lambda 2 to normal levels and reduced the residual JK by approximately 90% but failed to further decrease the Ka. According to these data, B mainly inhibits a coupled KCl passive self exchange plus a smaller active net KCl influx. Ou abolished the active component without affecting the passive self exchange. The presence of Na is necessary for the operation of the KCl-coupled self exchange, and Na gradients may provide the energy for the uphill KCl movements.

Animals↗
PubMed1986

Sodium compartmentalization of the arterial wall revisited: ouabain, temperature and enzymatic effects.

The sodium (Na) fractions of the dog carotid artery were identified by analyzing the effects of different procedures on 24Na washout curves. Although these never yielded more than three exponential terms, four Na fractions were identified. The fast-exchanging component amounted to 73 mmoles Na/kg w.wt., followed the kinetics of diffusion in a flat sheet with a diffusion coefficient of 6.9 X 10(-6) cm2 X s-1, and remained unaltered under the different experimental conditions. The intermediate component exchanged with a half time (t0.5) of 5.3 min and amounted to 18 mmoles Na/kg w.wt. About one third of this (6 mmoles) was constituted by cellular Na and the remaining by non-cellular Na, probably associated with extracellular structures. These two fractions could be discriminated by: (a) decreasing the rate of exchange of the cellular fraction with ouabain or low temperature (17 degrees C); (b) cell damage by freezing and thawing combined with metabolic poisoning; (c) enzymatic digestion of extracellular structures. When procedures (a) and (c) were combined, the intermediate component entirely disappeared. A third residual component amounted to 0.6 mmoles Na/kg w.wt and exchanged with a t0.5 of 70 min. It was unaffected by cellular damage or enzymatic digestion and was masked by the cellular phase in effluxes conducted at 17 degrees C or under ouabain. Its size decreased by microscopic dissection of the dense adventitia, which is probably its source.

Animals↗
PubMed1981

Acute saline expansion lowers blood pressure of early DOCA salt hypertensive rats.

Changes in blood pressure and body fluids volume caused by an acute saline load were studied in 6 normal and 7 DOCA-salt early hypertensive rats having normal inulin space and plasma volume. After loading, blood pressure increased in the normal group (+23 mm Hg) and fell (-17 mm Hg) in the DOCA-salt group. Expansion of extracellular fluid volume was similar in both groups but expansion of plasma volume was twice as high in the DOCA-salt than in the normal group. The results are compatible with an inhibition of a volume-sensitive vasopressor mechanism possibly involving vasopressin.

Animals↗
PubMed1981

Changes in vascular ionic composition at different stages of DOC-salt hypertension in the rat.

1. Sequential changes in the ionic composition of the aorta and skeletal muscle were followed during 1, 2 and 4-6 weeks in 30 rats given deoxycorticosterone (DOC) and salt supplemented with potassium chloride. Twenty-one rats, drinking water, were used as controls. 2. Twenty-five per cent of the test rats were hypertensive after 1 week, 60% after 2 weeks and 100% after 4-6 weeks. 3. Muscle potassium fell in all test rats by an average of 15%. In contrast, aortic potassium fell by 19% only in those rats which did not develop hypertension after 1 week. 4. Total and non-inulin sodium and water of the aorta were normal in rats which remained normotensive after 1 or 2 weeks and high in those which became hypertensive during the same period. 5. Total sodium and water content of the aorta were also high in rats which were hypertensive at 4-6 weeks. However, because of simultaneous expansion of the inulin space, non-inulin fractions were normal in this group. 6. Results suggest that vascular ionic changes participate in the pathogenesis of DOC-salt hypertension through more than a single mechanism.

Animals↗
PubMed1981

Glomerulotubular balance in hypertensive rats.

The relationship between glomerulotubular balance and the development of hypertension was studied in subtotally nephrectomized rats, with or without previous chronic salt loading, 1-4 weeks after the operation. The creatinine clearance (Ccr) was similarly reduced in all the groups as compared to control rats. The maximal glucose reabsorption (TmGlc) was also decreased in all experimental groups with the sole exception of saline-loaded hypertensive rats in which the fall did not reach the significance level. The ratio TmGlc/Ccr, which was taken as an index of glomerulotubular balance, was high in the hypertensive groups and further enhanced by saline loading. Peak values of TmGlc/Ccr were detected in the 1st week after operation and declined thereafter reaching normal levels in the hypertensive rats but not in the hypertensive saline-loaded animals. Results suggest that an early glomerulotubular imbalance is some way related to the development of hypertension in subtotally nephrectomized rats. This abnormality is apparently corrected by the counterbalancing effect of increased renal perfusion pressure but can be unmasked by saline loading.

Absorption↗
PubMed1980

A simple method for fitting multi-exponential curves of the decay type in a hand calculator.

The method of curve fitting here described is simple, dependable and can be programmed in a hand calculator. It consists in a log linear regression "peeling" that uses the maximization of the correlation coefficient for determining the number of exponential terms. It was experimentally verified and found to give satisfactory answers when compared to weighted least square iterative techniques.

Animals↗
PubMed1979

Pitfalls in kinetic studies of multiexponential decay processes with special emphasis on desaturation curves of arterial Na.

The purpose of this study was to detect and solve apparently trivial methodological flaws in experiments of the decay type which can invalidate any fitting procedure or compartmental analysis. The problems dealt with consisted in maintaining the steady state conditions defining the "true" starting time of the efflux and its optimal duration, determining the number of exponential terms and finding how many data points are necessary to identify them. The solutions proposed include avoidance of tissue blotting prior to the efflux, running a separate non effluxed sample, stopping the washout when the log plot of remaining and effluent counts becomes parallel, use of the optimization if the correlation coefficient for curve fitting and adequate the frequency of counting to the decay rate. Errors resulting from the failure to comply with these requirements are illustrated with samples.

Animals↗
PubMed1979

Effect of furosemide on the ionic composition of the arterial wall.

Furosemide decreased the intracellular H2O, Cl and K content and Cl concentration of dog carotid arteries incubated in normal or high K Krebs (123 mM). Cl loss exceeded K loss in normal Krebs but was of the same magnitude in high K Krebs. The findings are compatible with the inhibition of a neutral K-Cl coupled uptake.

Animals↗
PubMed1976

Correction of severe metabolic acidosis: a physiological approach.

1 - Five patients with severe metabolic acidosis secondary to methanol poisoning were studied before and after receiving 6.7 to 10 mEq NaHCO3/kg body weight. 2 - Two thirds of the infused HCO3- left the extracellular space and, since its apparent volume of distribution was much larger than under normal conditions, it largely overestimated HCO3- needs. On the contrary, the volume of distribution of the buffer base excess was found to be more stable and little affected by the acid-base status. 3 - Based on these observations, a simple method for estimating HCO3- needs in severe metabolic acidosis is proposed, requiring only the initial excess buffer base space which is calculated from body weight and blood buffer base excess values obtained before and after a first dose of bicarbonate.

Acidosis↗
PubMed1975

Changes in vascular ionic content and distribution across aortic coarctation in the dog.

Eight dogs were subjected to 80-90 percent coarctation of thoracic aorta, which produced a mean blood pressure gradient of 40 mmHg; six normal dogs were used as controls. Proximal aorta was compared with distal aorta, and carotid and femoral arteries removed after coarctation were compared against the contralateral vessels removed before coarctation. After 4 wk of coarctation, proximal aorta contained more total and intracellular Na (derived from 24Na fluxes and space measurements), more Mg, Cl, hydrolyzable SO4 equals to, and H2O than distal aorta. Hydrolyzable SO4 equals to was also higher in proximal than in distal noncoarcted aorta. Carotid arteries removed after coarctation had higher total and "noninulin" Na, higher Ca, and similar hydrolyzable SO4equals to and total hexosamine than the contralateral normal vessels. Aortic coarctation had no effect on ionic composition of femoral arteries. The data suggest that an increase in intravascular pressure has direct effects on vascular ionic composition. Although ionic changes may vary in different vessels, increased intracellular Na seems to be the most consistent finding.

Animals↗
PubMed1975

Anion effects on cation movements during correction of potassium depletion.

The differential effects of KCl vs. KHCO3 for intravenous K+ repletion were evaluated in a series of nephrectomized dogs previously depleted of 20% of total-body K by a 2-wk regimen consisting of K-free diet plus DOCA plus chlorothiazide. Twenty-four percent of K losses (5% of original TBK) were replaced by a 2-h infusion of either CKl or KHCO3. Blood pH was maintained at normal levels by controlling the rate of respiration. Skeletal muscle biopsies were taken before and 2 h after repletion, and blood samples were taken at intervals throughout. The following differences resulting from KHCO3 compared to KCl repletion were found: a) a greater cellular K uptake, a lower rate of increase, and a lower steady-state extracellular K+ concentration; b) a less increase in intracellular K+ concentration and a less decrease in intracellular Na+ concentration. These differences, which were independent of extracellular pH or kidney function, are thought to be secondary to unequal distribution of Cl- and HCO3-ions.

Animals↗
PubMed1975

Effect of ouabain on the renal response to furosemide.

The aim of this work was to investigate whether the natriuretic effect of furosemide can be wholly explained by the inhibition of a ouabain-sensitive Cl transport in the thick ascending limb of Henle. For this purpose 6 dogs undergoing moderate saline diuresis received 100 mug ouabain/kg into the left renal artery followed by 2 mg furosemide/kg IV. Urine was collected from both kidneys and blood samples taken at regular intervals. Ouabain produced a unilateral increase in Na excretion and little change in CCR and water and K excretion. IV furosemide increased Na, K and water excretion in both kidneys. Since Na excretion in the left kidney was already exhanced by ouabain the increment was lesser than in the right kidney. As a result water and electrolyte excretion became similar in both kidneys. Although ouabain did not prevent the renal response to furosemide, the effects of both drugs were not additive. This suggests that in addition to the thick ascending limb, furosemide acts in some other tubular segment which is insensitive to ouabain. Since furosemide is known to also inhibit passive Cl movements, a second site of action could be in the thin ascending limb of Henle, which lacks any active transport mechanism but is highly permeable to Cl.

Animals↗