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Biomedical subjects

A Bomzon

Publications and source records attributed to A Bomzon.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of bile duct manipulation and pair-feeding on peripheral vascular neuroeffector mechanisms: in vitro studies.

Investigators studying the pathophysiological sequelae of bile duct ligation use different species of laboratory animals at varying postoperative times. There is also considerable variation in the type of control animal used for these experiments. In this study, we have attempted to validate our choice of the 3-day bile-duct-manipulated rat as the most appropriate control to study peripheral vascular neuroeffector mechanisms in bile-duct-ligated rats. We have compared the in vitro contractile response to norepinephrine in the absence and presence of cocaine, and the accumulation of the amine using 3H-norepinephrine of arterial rings and portal veins prepared from three different types of control rats--unoperated control, the 3-day bile-duct-manipulated and the 3-day pair-fed, bile-duct-manipulated rats. In vitro arterial reactivity to norepinephrine in the sham-operated rats was significantly attenuated and was associated with a cocaine-sensitive increase in norepinephrine uptake. Portal veins from the same animals showed no changes in in vitro reactivity to norepinephrine, although bile-duct manipulation and pair-feeding enhanced amine uptake. This study has demonstrated that bile-duct manipulation and pair-feeding attenuate in vitro vascular reactivity and enhance norepinephrine uptake. These in vitro changes are more pronounced in arterial tissue than venous tissue. In conclusion, these data indicate that bile-duct manipulation is the control of choice when measuring in vitro vascular neuroeffector mechanisms in 3-day bile-duct-ligated rats. Furthermore, these data emphasize the need to validate the control when experiments involving bile-duct ligation are undertaken.

Animals↗
PubMed1995

Effects of sodium status on the venous response to noradrenaline infusion in pre-ascitic cirrhosis.

1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response (Rmax.) and the dose of noradrenaline that yielded 50% of Rmax. (ED50) were then calculated. 2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 +/- 0.14 mm) compared with a high sodium (2.57 +/- 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. Rmax. was not significantly different in either group on both diets. With low sodium intake, ED50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED50 (34.4 +/- 7.4 ng/min) than the cirrhotic patients (5.03 +/- 0.86 ng/min; P < 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 +/- 0.11 nmol/l) to a high (0.68 +/- 0.09 nmol/l; P < 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets. 3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.

Adult↗
PubMed1995

Vasodilatory responses of isolated arteries of cirrhotic rats.

1. There is currently considerable interest in the role of locally produced vasodilators such as nitric oxide and adenosine in the pathogenesis of the peripheral vasodilatation of cirrhosis. However, the signal transduction pathways involving guanylate cyclase and adenylate cyclase have not been clearly delineated in the isolated blood vessel. 2. We therefore aimed to examine the in vitro vasorelaxant effects of the endothelium-dependent dilator bethanechol, the endothelium-independent dilator sodium nitroprusside and adenosine, as drugs that work via activation of guanylate and adenylate cyclases, in isolated aortic and superior mesenteric arterial rings from cirrhotic and control rats. 3. Cirrhosis was induced by chronic bile duct ligation and section of 24-28 days' duration, while controls underwent sham operation. The vessels were precontracted with the alpha 1-adrenoceptor agonist phenylephrine, then relaxed by incremental doses of the three drugs. 4. Marked attenuation of vasoconstriction induced by phenylephrine in isolated aortic and mesenteric arterial rings from cirrhotic rats compared with the control vessels was observed. 5. There were no significant differences in relaxation between the cirrhotic and control vessels to the three drugs. We conclude that in vitro vasodilatory responses mediated through signal transduction pathways involving guanylate cyclase and adenylate cyclase remain unchanged in a rat model of biliary cirrhosis.

Adenosine↗
PubMed1995

Epinephrine dose-response of the isolated working heart in O2-exposed rats.

BACKGROUND: Heart energy efficiency, which is affected by catecholamines, has previously been shown to decline in rats with prolonged normobaric O2 exposure. HYPOTHESIS: Oxygen exposure affects dose response of the heart to catecholamines. METHODS: Epinephrine dose-response (10(-10) - 5 x 10(-6) mol.L-1) was measured in the isolated working heart excised from control rats breathing air, and rats exposed to normobaric 100% oxygen for either 24 h or 49 h. The variables measured were input (oxygen consumption (VO2) and output power, cardiac contractility (Emax and maximal dP/dT), coronary resistance, heart frequency (fH) and left ventricular pressure. Variable (Y*) dose response to epinephrine concentration (C) was fitted to the equation: Y* = Ymax/(1 + (C/C50)n), Ymax--maximal Y*, C50--C for half Ymax and n--an empirical power. RESULTS: Oxygen exposure of the intact rat had little influence on baseline cardiac variables, but did affect sensitivity to catecholamines. A general effect of the O2 exposure was a left shift of the dose-response curve for example, C50 was reduced by 72, 41 and 43 x 10-8 mol.L-1 for VO2, fH and Emax, respectively, after the 24 h exposure. CONCLUSIONS: There was a pronounced change in the dose-response in hearts from 24 h O2-exposed rats, a change partially reversed in hearts from 49 h O2-exposed rats. The high dose, which had a stimulatory effect on hearts from control rats, failed to stimulate hearts from hyperoxic rats.

Adrenergic alpha-Agonists↗
PubMed1994

Pulmonary angiotensin converting enzyme activity in elastase induced emphysema.

Pulmonary emphysema would be expected to reduce angiotensin converting enzyme (ACE) activity due to diminished capillary bed. However, transpulmonary angiotensin conversion has been found to be unaffected or marginally reduced in emphysema. In the present study we examined the activity of ACE in an experimental model of emphysema. Vmax and Km of ACE were determined in lung homogenates of six hamsters with elastase-induced emphysema and seven control hamsters. In the emphysematous lungs, ACE activity was significantly elevated due to marked increase in Vmax (19.2 +/- 1.7 vs. 4.9 +/- 1.6 nmol/min/mg protein for emphysematous and control lungs, P < 0.01). The Km of ACE was unaffected by emphysema. We suggest that the increase in ACE activity may be an adaptive change to enable adequate metabolic activity in the face of progressive reduction in pulmonary capillary surface area in emphysema.

Amino Acid Sequence↗
PubMed1993

Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi.

To evaluate if L-arginine-nitric oxide-pathways are involved in the neural relaxation of the sphincter of Oddi, we studied the effect of nitric oxide synthase inhibition on electrical field stimulation-induced relaxation of the sphincter of Oddi in the guinea pig in vitro. After incubation with atropine (1 microM), phentolamine (1 microM) and propranolol (1 microM), histamine (50 microM) and cholecystokinin-octapeptide (25 nM) produced similar increases in sphincter tone. Subsequent field stimulation induced sphincteric relaxation, that was significantly greater when the initial tone had been raised by cholecystokinin (5 Hz, 59 +/- 9%; 10 Hz, 79 +/- 9%) compared to histamine (5 Hz, 27 +/- 3%; 10 Hz, 40 +/- 7%). N-omega-Nitro-L-arginine methyl ester (L-NAME, 100 microM), which competitively inhibits nitric oxide synthase, markedly suppressed this relaxation. The subsequent addition of L-arginine (1 mM), but not D-arginine (1 mM), restored the relaxation. Hexamethonium (100 microM) did not affect the relaxation, but tetrodotoxin (1 microM) completely abolished it. Sodium nitroprusside caused a dose-dependent relaxation of the sphincter (ED50 13 nM), which was unaffected by L-NAME. In conclusion, endogenous nitric oxide synthase products represent a major transmitter of non-adrenergic non-cholinergic relaxation of the sphincter of Oddi in the guinea pig. This relaxation is partially facilitated by cholecystokinin.

Amino Acid Oxidoreductases↗
PubMed1993

Hypotension in experimental cirrhosis. Is loss of vascular responsiveness to norepinephrine the cause of hypotension in chronic bile-duct-ligated dogs?

It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra-arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile-duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham-operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1993

Cardiac function and responsiveness to beta-adrenoceptor agonists in rats with obstructive jaundice.

The function and role of the heart and the contribution of cardiac beta-adrenoceptors in the pathogenesis of circulatory failure in obstructive jaundice were studied in the 3-day bile duct-ligated (BDL) rat using three different techniques to measure cardiac function and beta-adrenoceptor activity, number, and affinity. The techniques were the pithed rat preparation, the isolated working heart preparation, and a competitive radioligand binding assay for beta-adrenoceptors. The results of these experiments were compared with those obtained in 3-day bile duct-manipulated (sham operated; SO) rats. Impaired indexes of basal cardiac contractility were observed in the BDL pithed rats and isolated working hearts. In these two preparations, responsiveness to norepinephrine and the beta-adrenoceptor agonists, isoproterenol and dobutamine, was unaffected by bile duct ligation. The affinity and number of cardiac beta-adrenoceptors in membranes from the hearts of SO and BDL rats were not significantly different from each other. These experiments have established for the first time that the 3-day BDL rat has a cardiac myopathy associated with intact responsiveness to beta-adrenoceptor agonists, a normal unchanged affinity and number of cardiac beta-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1993

Peripheral vascular neuroeffector mechanisms in experimental cholestasis.

Jaundiced patients have systemic hypotension and are more susceptible to hemorrhagic shock than nonjaundiced individuals. We have hypothesized that the mechanism whereby these cardiovascular complications arise is linked to a disturbance of the vascular neuroeffector process in the cardiovascular system. With the use of 3-day bile duct-manipulated (sham-operated) and bile duct-ligated rats, we have evaluated alpha-adrenoceptor function and amine uptake using in vivo and in vitro techniques. Blunted pressor responsiveness to norepinephrine, electrical stimulation, and the alpha 1-adrenoceptor agonists, methoxamine and phenylephrine, was observed in the bile duct-ligated pithed rats. In contrast, normal responsiveness to BHT-933 and clonidine, the alpha 2-adrenoceptor agonists, was seen in these animals. The uptake 1 blocker, cocaine, caused potentiation of equal magnitudes of the pressor responsiveness to electrical stimulation and norepinephrine in the sham-operated and bile duct-ligated pithed rats. In aortic rings prepared from the bile duct-ligated rats, blunted in vitro vascular reactivity to norepinephrine and the same alpha 1-adrenoceptor agonists was seen. Bile duct ligation had no effect on norepinephrine uptake or its kinetics in stressed and unstressed arterial rings and portal veins. We have thus concluded that bile duct ligation induces a defect in the functional expression of cardiovascular alpha 1-adrenoceptors without any effects on the activity of alpha 2-adrenoceptors or norepinephrine uptake.

Adrenergic alpha-Agonists↗
PubMed1992

The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.

The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.

Animals↗
PubMed1992

Pressor response to a postural change in cirrhosis: an experimental study in the CCl4-treated rat.

1. Systemic hypotension, blunted cardiovascular responsiveness to noradrenaline and an abnormal hypertensive pressor response to a postural change have been described in cirrhotic patients. 2. We have examined the role of blunted responsiveness in these abnormalities by studying basal arterial blood pressure and its response to a postural change (vertical head-up 90 degrees tilting) in conscious and pithed CCl4-treated (cirrhotic) rats, as well as assessing the pressor response to noradrenaline in vivo and the vascular contractile response to noradrenaline in vitro. 3. A diminished hypotensive response to a change in posture was found in pre-cirrhotic portal hypertensive rats, whereas an inverted hypertensive pressor response in the face of systemic hypotension occurred in the cirrhotic rats with portal hypertension. 4. The inverted pressor response was abolished in the pithed portal hypertensive cirrhotic rats. 5. The pressor response to noradrenaline in vivo in conscious cirrhotic rats and the vascular contractile responsiveness to noradrenaline in vitro were intact. 6. We conclude that blunted responsiveness to noradrenaline is not a contributory factor to the development of systemic hypotension or the inverted pressor response to a change in posture in cirrhosis.

Animals↗
PubMed1992

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow.

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration-response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6) M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cardiovascular responses to serotonin in experimental liver disease.

Recent evidence suggests that serotonergic mechanisms within the cardiovascular system are activated and may be important in the development of the hyperkinetic circulation and the maintenance of portal hypertension in cirrhotic patients. The in vivo pressor and positive chronotropic response together with the in vitro contractile responses of aortic rings and portal veins to serotonin were studied in three different rat models of cirrhosis, portal hypertension and jaundice: the portal vein-ligated rat, the carbon tetrachloride-induced cirrhotic rat, the chronic bile duct-ligated cirrhotic rat and the 3-day noncirrhotic, nonportal hypertensive-jaundiced rat. In addition, the activity of the enzyme monoamine oxidase type A was determined in lung homogenates prepared from the four groups of sham and treated animals. In the four different groups of sham-treated or operated pithed rats, serotonin caused a dose-dependent increase in mean arterial blood pressure without any effect on the heart rate. The pressor responses to serotonin in the three models of portal hypertension were significantly attenuated from their respective sham group. In the 3-day noncirrhotic, nonportal hypertensive-jaundiced rats, the pressor response was no different than that seen in the sham-operated rats. No evidence of consistent potentiated or blunted in vitro reactivity to serotonin of arterial rings and portal veins from the four groups of rats was seen. Portal hypertension, cirrhosis and hyperbilirubinemia had no effect on the activity of monoamine oxidase type A. These data demonstrate that portal hypertension is associated with an attenuated pressor response to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease.

Animals↗
PubMed1990

Anesthesia and pressor responsiveness in chronic bile-duct-ligated dogs.

Cardiovascular homeostasis is comprised under general anesthesia and in jaundice. Because surgery is often performed on jaundiced patients, it is not altogether surprising that the incidence of perioperative complications is higher in such patients than in nonjaundiced ones. In this study we assessed the potential synergistic effects of anesthesia and jaundice on cardiovascular responsiveness of chronic bile-duct-ligated dogs. Responsiveness to norepinephrine, angiotensin II and isoproterenol was determined before and after chronic bile-duct ligation or sham-operation while the dogs were conscious or under halothane, fentanyl or pentobarbital-sodium anesthesia. These data have shown that halothane- and barbiturate-induced anesthesia do not alter mean arterial blood pressure in unoperated dogs when compared with conscious dogs before laparotomy. Furthermore, these two agents did not modify the pressor, dilator and positive inotropic responses to intravenous infusions of norepinephrine, angiotensin II and isoproterenol. Fentanol, however, reduced mean arterial blood pressure and heart rate without influencing responsiveness to the three vasoactive agents. Blunted responsiveness in the chronic bile-duct-ligated dogs to the three vasoactive agents was observed without any marked changes in mean arterial blood pressure or heart rate. The same blunted responses observed in the conscious, chronic bile-duct-ligated dogs were also seen in the anesthetized, chronic bile-duct-ligated dogs. Halothane caused a marked hypotensive effect in the chronic bile-duct-ligated dogs that was not seen in the sham-operated dogs. Conscious and anesthetized sham-operated dogs responded in the same manner as the conscious and anesthetized dogs before ligation. (ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1990

Angiotensin-converting enzyme activity in the isolated perfused guinea pig lung.

We have developed a pressure-dependent isolated lung perfusion system that can be used for the determination of pulmonary enzyme activity and kinetics under physiologic conditions. This development was done using two different artificial radiolabeled substrates, glycine-1-hippuryl-L-histidyl-L-leucine and phenyl-4(n)-hippuryl-glycyl-glycine, for the pulmonary enzyme, angiotensin-converting enzyme. With this system, we assessed the effects of different perfusate types upon the stability of the perfusion as well as the independent effects of pressure, flow, and substrate concentration on the activity of this enzyme. We concluded that this system enables the operator to determine the kinetics and activities of pulmonary enzymes independently of the effects of pressure and flow in a perfusion system that is stable for at least 3 h under physiologic conditions.

Animals↗