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Biomedical subjects

I Leusen

Publications and source records attributed to I Leusen.

At least 55 records · Page 3Linked to original sources
PubMed1983

Influence of prostaglandin-synthesis inhibitors on carbachol- and histamine-induced vasodilatation in perfused rat hindquarters.

In perfused rat hindquarters, in which vascular tone was maintained by norepinephrine, carbachol-induced dilatations were blocked by atropine (10(-7) M), while histamine dilatations were inhibited as well by mepyramine (10(-6) M) as by cimetidine (10(-5) M) indicating a histamine effect through both H1- and H2-receptors. This double-receptor histamine effect was confirmed by the observation that specific H1- and H2-receptor agonists, respectively PEA (2-pyridyl-ethyl-aminedihydrochloride) and dimaprit also produced a vasodilatation. Carbachol- and histamine-induced dilatations were also inhibited by ETYA (5,8,11,14-eicosatetraynoic acid) and quinacrine but not by indomethacin. The inhibition of the histamine vasodilatation appeared to rest on an interference with the H1-receptor mechanism. It is concluded that metabolites of arachidonic acid possibly mediate the dilating effect of carbachol, acting through muscarine receptors, and of histamine, acting through H1-receptors.

Animals↗
PubMed1983

Role of the endothelium in the vasodilator response of rat thoracic aorta to histamine.

Despite their potent vasodilating action in vivo, acetylcholine and histamine often show a vasoconstricting action in vitro. As the endothelium has an important role in the vasodilating effect of acetylcholine, we investigated the possible role of the endothelium in the vasodilating effect of histamine in comparison to acetylcholine. Experiments were done on ring segments of rat thoracic aorta mounted for isometric tension measurements. We demonstrated that relaxation by histamine and acetylcholine of pre-contracted rat aorta segments required the presence of endothelial cells. Acetylcholine acting on muscarinic receptors, and histamine acting on H1-receptors seemed to initiate the production of mediator(s) from the endothelial cells, which leads to relaxation of the vascular smooth muscle cells. This production appeared to be depressed by ETYA and hydroquinone, and under hypoxic conditions.

Acetylcholine↗
PubMed1983

Correction of CSF HCO-3 after its experimental increase in normocapnia: inhibition by acetazolamide.

In anaesthetized normocapnic dogs CSF [HCO-3] was increased to ca 33 mmol/l by perfusing the brain ventricles for 45 min with a mock CSF containing a high [HCO-3] which in addition contained 2.5 mg/ml acetazolamide to inhibit central carbonic anhydrase. In dogs with normal plasma [HCO-3], CSF [HCO-3] fell by 5.4 mmol/l in 2 h following the end of the perfusion. Lowering plasma [HCO-3] to 11 mmol/l by infusing HCl intravenously increased the CSF [HCO-3] fall to 7.5 mmol/l. Increasing plasma [HCO-3] to 36 mmol/l completely impeded the fall in CSF [HCO-3]. It is concluded that in these experiments clearing of HCO-3 from the CSF is critically dependent on plasma [HCO-3]. When the data are compared to those of comparable experiments without intraventricular administration of acetazolamide (Weyne et al. 1982), they indicate that acetazolamide impedes clearing of HCO-3 from CSF at high and at normal plasma [HCO-3] but not at low plasma [HCO-3]. The experiments therefore suggest a dual contribution for the clearing of HCO-3 from the CSF after its experimental increase: diffusion along the CSF-plasma gradient for HCO-3 and a carbonic anhydrase dependent clearing of HCO-3.

Acetazolamide↗
PubMed1983

Identification of testosterone and progesterone in hemolymph of larvae of the fleshfly Sarcophaga bullata.

Testosterone- and progesterone-like substances were detected by radioimmunoassay (RIA) in chromatographed extracts of hemolymph from larvae of Sarcophaga bullata (S.B.). Gas chromatographic (GC) analysis after heptafluorobutyric acid (HFBA) derivation of hemolymph extracts, purified by paper and silica gel column chromatography, showed a peak in the GC recordings with the same retention time as the HFBA derivative of pure testosterone. A testosterone concentration of 92 ng/100 ml hemolymph was found by GC; the concentration of progesterone, calculated on the basis of the RIA, was about two times higher. After preparing the o-pentafluorobenzyloxime (OPFB)-heptafluorobutyryl ester (HFB) derivatives of the hemolymph extracts, negative ion chemical ionization capillary gas chromatography-mass spectrometry (NCI/GC-MS) proved that hemolymph of larvae of the fleshfly Sarcophaga bullata indeed contains testosterone and progesterone. Several metabolites and precursors of the latter compounds could also be detected during the NCI/GC-MS analyses. Estrogens could not be traced by any of the methods we used. This is the first time that these steroids have been identified in insect hemolymph. These results add interesting perspectives for comparative endocrinology.

Animals↗
PubMed1983

Changes in brain ECF pH during metabolic acidosis and alkalosis: a microelectrode study.

We used pH-sensitive double-barreled microelectrodes to measure brain extracellular fluid (ECF) pH in anesthetized dogs during isocapnic infusion acidosis (HCl) and alkalosis (Na2CO3) of 45-60 min duration. The diameter of the tips of these electrodes varied from less than 1 to 27 micron and were placed 5 mm below the surface of the parietal cortex. In group I (metabolic acidosis, n = 5) mean plasma and brain ECF pH fell significantly by 0.221 and 0.025, respectively, with changes in brain ECF pH being 11.3% of those noted in plasma. In group II (metabolic alkalosis, n = 5) mean plasma and brain ECF pH rose significantly by 0.170 and 0.049, respectively, with changes in brain ECF pH being 28.8% of those noted in plasma. Mean arterial and sagittal venous PCO2 and cisternal cerebrospinal fluid (CSF) acid-base variables did not change significantly during acid or base infusion. We conclude that during transients of isocapnic metabolic acid-base perturbations ionic gradients exist between brain ECF and CSF and that changes in brain ECF pH measured by microelectrodes follow the changes in plasma pH. These pH changes may play an important role in respiratory adaptations of acute metabolic acidosis and alkalosis.

Acidosis↗
PubMed1982

Correction of CSF HCO(-3) after its experimental increase in normocapnia. Role of plasma HCO(-3).

In anesthetized normocapnic dogs CSF [HCO(-3)] was increased to 33 mmol/l by perfusing the brain ventricles for 45 min with a mock CSF containing a high [HCO(-3)]. In dogs with normal plasma [HCO(-3)], CSF [HCO(-3)]fell by ca. 7 mmol/l in 2 h following the end of the perfusion. Lowering plasma [HCO(-3)] to 11 mmol/l by infusing HCl intravenously was without effect but increasing plasma [HCO(-3)] to 36 mmol/l by infusing Na2CO3 limited the CSF [HCO(-3)] fall to 2.8 mmol/l. It is concluded that correction of CSF [HCO(-3)] is partially dependent on a sufficiently low plasma [HCO(-3)]. The small and persistent fall of CSF [HCO(-3)] which at high plasma [HCO(-3)] occurs against a concentration gradient with blood suggests moreover the contribution of more specific mechanism(s) for lowering CSF [HCO(-3)] after its experimental increase.

Acid-Base Equilibrium↗
PubMed1981

pH aspects of transient changes in conduction velocity in isolated heart fibers after partial replacement of chloride with organic anions.

Conduction velocity in isolated rabbit atrial fibers was continuously measured in solutions having a different anionic composition. When 20mmol/l of chloride was replaced by 20 mmol/l lactate or other anions of weak organic acids at constant pH 6.8, biphasic initial transient changes in conduction velocity were observed. The produced transient changes had a greater amplitude with organic acids which have a greater pK and lipid/water partition ratio. The magnitude of the transients was also greater at pH 6.8 than at pH 7.5, and also when the buffering capacity of the superfusion solution was smaller. Measurements of intracellular pH (pHi) in sheep Purkinje fibers and of pH at the surface (pHs) of sheep Purkinje and rabbit atrial fibers with pH sensitive microelectrodes, showed a transient increase of pH and a sustained decrease of pHi on replacement of 20mmol/l chloride by organic anions of weak acids (at constant pH of the superfusion solution). A combined influence of the transient pHs change and the sustained pHi modification seems to be important in the explanation of the biphasic changes in conduction velocity.

Animals↗
PubMed1981

Role of testosterone levels and of hypophysis in the HCG-induced modifications of the 7 alpha-hydroxylation and 5 alpha-reduction processes in incubated rat testes.

The role of a direct or a hypophysis-mediated influence of increased testosterone levels in the effects of a long-term high-dose HCG administration (10 IU/day) upon the 7 alpha-hydroxylation and 5 alpha-reduction activities of incubated testes of mature rats was investigated. Administration of high doses of HCG to hypophysectomized rats resulted in the same metabolic changes as in normal rats, namely, a large decrease in the 7 alpha-hydroxylation and an increase in the 5 alpha-reduction processes. Administration of testosterone-propionate (0.2 mg and 20 mg/day) for several days to hypophysectomized rats and to normal rats receiving and substitutive dose of 1 IU HCG/day, did not modify the testicular metabolization pattern. These findings indicate that the decrease in testicular 7 alpha-hydroxylation activity induced by long-term administration of high doses of HCG is probably not mediated by the hypophysis nor by the extracellular testosterone levels.

Androgens↗
PubMed1980

Kinetic study of HCG induced decrease of microsomal 7 alpha-hydroxylase activity in rat testes.

Microsomes from rat testes were incubated with varying concentrations of 14C labelled testosterone and androstenedione. The production of 7 alpha-hydroxytestosterone and 7 alpha-hydroxyandrostenedione was followed; Km and Vm values were calculated from Lineweaver-Burk curves. A sustained treatment of rats with HCG resulted in a considerable decrease of the maximal 7 alpha-hydroxylation rats (Vm) whereas the Km value was not changed. Vm of microsomes from normal rats, when incubated with microsomes from HCG-treated animals, was also decreased substantially. It is concluded that HCG-induced depression of 7 alpha-hydroxylation capacity of testicular microsomes is at least in part due to non-competitive inhibition of the enzyme.

Androstenedione↗
PubMed1980

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs.

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.

Animals↗
PubMed1980

Role of medullary hemodynamics in the natriuresis of drug-induced renal vasodilation in the rat.

In contrast to most renal vasodilators, such as acetylcholine (ACh), secretin increases renal blood flow in the dog without a marked effect on sodium excretion (UNaV). To investigate this observation, we studied the relationship between renal vasodilation, UNaV, and papillary plasma flow (PPF) in rats, infused either with ACh or secretin into the aorta at the level of both renal arteries. ACh significantly increased GFR, PAH clearance, and UNaV (delta + 0.35 ml/min, + 2.11 ml/min and + 1.77 muEq/min, respectively; P < 0.05). PPF rose from 50 +/- 2.6 ml/min 100 g (mean +/- SE) in control rats to 91 +/- 4.7 ml/min 100 g after ACh (p < 0.001). Despite a similar increase in PAH clearance after secretin (+ 2.21 ml/min; P < 0.01), UNaV remained unchanged and PPF was only slightly, although significantly, increased (from 50 +/- 2.6 ml/min 100 g to 65 +/- 2.75 ml/min 100 g; P < 0.05). Both total kidney and papillary vasodilation, and the increase in UNaV after ACh were blocked by previous administration of meclofenamate (M), a prostaglandin inhibitor. No effect of M in secretin-infused rats was observed. In conclusion, the relationship between a total renal vasodilation and natriuresis was dissociated with secretin, but not with ACh. However, a relationship between the natriuresis and influence on papillary hemodynamics was observed with both vasodilators. Finally, the renal hemodynamic and natriuretic effects of ACh are probably mediated by prostaglandin release.

Acetylcholine↗
PubMed1980

The effect of prostaglandin synthesis inhibitors on sodium excretion in the awake rat during acute water and isotonic Ringer loading.

Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally different inhibitors of prostaglandin synthesis were employed and studies were performed in conscious rats allowed to recover from prior surgical instrumentation. Either meclofenamate (5 mg/kg) or indomethacin (5 mg/kg) was given to unanesthetized rats undergoing either a saline diuresis (n = 24, group A) or a water diuresis (n = 27, group B). In a third group (n = 27, group C) the drugs were given during hydropenia at the onset of a massive volume expansion (10% BW over 60 min). GFR, PAH clearance, absolute (UNaV) and fractional sodium excretion (FENa) and urinary prostaglandin E2 and F2 alpha excretion were measured, after prostaglandin inhibitor or placebo injections. In group A, renal function and UNaV or FENa were not altered by indomethacin or placebo injection despite a 50% fall in both UPGE2 and UPGF2 alpha excretion after prostaglandin inhibitors. Meclofenamate produced a fall in PAH clearance from 27.0 to 21.2 ml/min. kg with a decrease in UNa V from 64.7 to 44.3 microEq/min, kg (p < 0.05). In group B, the administration of either prostaglandin inhibitors or placebo did not alter GFR, PAH clearance, UNa V or FENa despite a decrease in UPG excretion with 48% after PG inhibitors. In group C, the rise in FENa after acute volume expansion was similar in prostaglandin inhibited rats compared to placebo injected animals (delta FENa was 6.67% after placebo, 5.85% after meclofenamate and 6.03% after indomethacin, respetively; p > 0.05). However, both meclofenamate and indomethacin adminsitration blunted the rise in GFR, PAH clearance, UPGE2 and UPGF2 alpha excretion normally observed during volume expansion in the placebo injected rats. Thus, these findings seem to indicate that endogenous intrarenal prostaglandins are not important determinants of the natriuretic response to an acute expansion of the extracellular volume. They do not give persuasive evidence that renal praostaglandin production and renal sodium excretion are closely interrelated or interdependent.

Animals↗