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Biomedical subjects

W Rascher

Publications and source records attributed to W Rascher.

At least 289 records · Page 16Linked to original sources
PubMed1979

Vascular reactivity in the pathogenesis of spontaneous hypertension.

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar-Kyoto (WK) rats; dose-response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.

Angiotensin II↗
PubMed1979

A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats.

1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.

3-Mercaptopropionic Acid↗
PubMed1979

Effect of neonatal sympathectomy by 6-hydroxydopamine on volume and resistance regulation in stroke-prone spontaneously hypertensive rats.

1. Neonatal sympathectomy with 6 hydroxy-dopamine (6-OHDA) was used as a tool to assess the significance of an increased sympathetic vascular tone for the development of high blood pressure in stroke-prone spontaneously hypertensive rats. After administration of 6-OHDA the rise in blood pressure was blunted for the following 9 weeks until innervation was re-established. 6-OHDA-treated rats retained more sodium and had larger plasma and blood volumes than sham-treated rats. 2. Catecholamines in plasma were increased 2-10-fold immediately after sympathectomy, but their concentrations were subnormal on day 7. Eight weeks after sympathectomy plasma noradrenaline and dopamine were not elevated, but plasma adrenaline has increased twofold. 3. The reactivity of resistance vessels to noradrenaline was markedly enhanced and the neuronal uptake and metabolism of noradrenaline were still reduced 8 weeks after neonatal sympathectomy. 4. These results confirm the significance of an intact sympathetic nervous system for the development in these rats. Sodium retention and increased plasma and blood volume may be considered as a compensatory mechanism for the vasodilatation resulting from decreased vasomotor tone.

Animals↗
PubMed1979

Modulation of sympathetic vascular tone by prostaglandins in corticosterone-induced hypertension in rats.

1. In corticosterone-induced hypertension in rats the activity of the peripheral sympathetic nervous system and its modulation by prostaglandins was studied. 2. Plasma concentrations of noradrenaline were reduced if compared with those in normotensive control rats. 3. The sensitivity of the isolated perfused hind-limb preparation to noradrenaline was enhanced before blood pressure rose and increased further with the development of hypertension. 4. Arachidonic acid, prostacyclin (prostaglandin I2), but not 6-keto-prostaglandin F1 alpha, reversed the supersensitivity to noradrenaline. 5. These results suggest that corticosterone induces a supersensitivity to noradrenaline by inhibiting the biosynthesis of prostaglandins. Changes in the sensitivity of the vascular smooth muscle may play a role in the development of glucocorticoid hypertension.

Animals↗
PubMed1978

Reversal of renal hypertension: effects on renin, salt and water balance.

The effect of removal of one renal artery stenosis on renal sodium and fluid excretion and on the activity of the renin-angiotensin system (RAS) has been investigated in three types of renal hypertension of rats. Blood pressure fell in all experimental models after declamping, independently of changes in urinary sodium and water excretion or plasma angiotensin II (ANG II). Plasma concentrations of ANG II did not rise in response to salt and fluid loss induced by declamping when the contralateral kidney had been removed or when it was depleted from renin. A high renin content of the declamped kidney prevented major salt and fluid loss, whereas renin depletion of this kidney was accompanied by an exaggerated natriuresis and diuresis. Besides this tubular modulation of renal salt and water handling by the local RAS, glomerular filtration rate could be reduced by a stimulated activity of this system in plasma, indicated by a close relationship between serum urea and plasma ANG II levels.

Angiotensin II↗
PubMed1978

Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus.

Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.

Angiotensin II↗
PubMed1978

Effects of beta-adrenergic blocking agents on peripheral vascular resistance.

The effects of the beta-adrenergic blocking agents propranolol, pindolol, atenolol, bunitrolol, and methypranol on the vascular resistance of isolated perfused hindlimbs of rats were investigated. At concentrations of 0.01 microgram/ml in the perfusate dl-propranolol and pindolol significantly increased vascular resistance by blockade of beta2-receptor mediated vasodilatation, whereas atenolol, bunitrolol and methypranol had no effect on peripheral resistance at this concentration. With increasing concentrations up to 10 microgram/ml all drugs, with the exception of atenolol, caused vasodilatation. We conclude that the specificity of beta-blocking agents can be established in the isolated perfused hindlimb vasculature of rats through its effect on vascular resistance. The lack of inhibition of vascular beta2-receptors at low concentrations of atenolol and also bunitrolol and methypranol show relative selectivity for beta1-receptors. The differential effects of beta-adrenergic agents on vascular resistance may have significance for the clinical use of the drugs.

Adrenergic beta-Antagonists↗
PubMed1976

Measurement of two plasma triglyceride lipases by an immunochemical method: studies in patients with hypertriglyceridemia.

Postheparin plasma lipolytic activity consists of two hydrolytic activities, hepatic triglyceride lipase and lipoprotein lipase. These two enzymes were separated and partially purified by means of ammonium sulfate precipitation and affinity chromatography using Sepharose with covalently linked heparin and concanavalin A, respectively. Antibodies were produced against hepatic triglyceride lipase and they did not cross react with lipoprotein lipase. Optimal conditions for selective precipitation of hepatic lipase and specific measurement of these two lipases were investigated. This method was applied to the study of 15 patients with hypertriglyceridemia and 8 patients with familial lecithin-cholesterol-acyltransferase deficiency of whom 6 also had a marked elevated plasma triglyceride concentration. All patients had normal values of hepatic plasma lipase. All 8 patients with Type I and 2 of 4 patients with Type V hyperlipoproteinemia had lipoprotein lipase activities that were markedly reduced. The patients with Type III hyperlipoproteinemia and all 8 patients with lecithin-cholesterol-acyltransferase deficiency also had normal lipoprotein lipase values. These studies emphasize the necessity for differentiating between triglyceride lipase activity of hepatic and extrahepatic origin in evaluating patients with impaired triglyceride metabolism.

Acyltransferases↗
PubMedDate not supplied

Plasmatic [corrected] factor XIII reduces severe pleural effusion in children after open-heart surgery.

Chylous effusions frequently occur after cardiac surgery due to severe damage to the lymphatic system, thus indicating that the insertion of a chest tube may be necessary. Factor XIII (FXIII) is discussed as being essential for wound healing. The aim of this retrospective study was to evaluate whether the application of a single dose of FXIII results in a reduced amount of pleural effusion, leading to an earlier release of patients from the hospital. The cases of 40 children with severe chylous effusions after open-heart surgery were examined. Twenty patients received FXIII and were compared to 20 age- and weight-matched patients who did not receive FXIII. Major parameters included the amount of effusion before and 1 and 3 days after the application of FXIII; the duration of chest tubes; the total amount of fluid loss via drainage; and the period of hospitalization. FXIII levels in plasma showed an inverse correlation with fluid loss. After application of a single dose of FXIII, a significant reduction of pleural effusion within the first 24 hours was detected. However, no difference was observed between the two groups when comparing the total amount of pleural effusions within the first 72 hours. Finally, the duration of hospitalization did not differ between the FXIII-treated and the control group. A single application of FXIII rapidly reduces the amount of chylous effusions in the early period after open-heart surgery. This effect is detectable only for 24 hours after the treatment and does not alter the further clinical outcome. Prospective clinical trials are warranted to determine if repeated application or a higher dose of FXIII may improve the clinical outcome of chylous leakages in children after open-heart surgery.

Case-Control Studies↗
PubMedDate not supplied

[Acute reversible kidney failure in IgA nephritis].

Four patients with acute renal failure during an acute course of IGA-nephritis are described. Percutaneous renal biopsies showed only minor glomerular lesions in all patients. Immunosuppressive therapy was not necessary. In all patients acute renal failure was completely reversible. The four patient showed further episodes of macrohematuria without acute renal failure. All patients had normal renal function, normotensive blood pressure and microhematuria during interval. In three of the patients we found erythrocytes casts and a mild protein excretion. IGA-nephritis is one of the most common types of glomerulonephritis in adolescents and adults. If acute renal failure occurs during a course of IGA-nephritis with macroscopic haematuria a percutaneous renal biopsy has to be performed. Only in case of severe crescents formation (greater than 75%) immunosuppressive therapy is necessary. Glomerular lesions are responsible for long time prognosis.

Acute Kidney Injury↗
PubMedDate not supplied

Contribution of the sympathetic nervous system to the centrally-induced pressor action of angiotensin II in rats.

1. Angiotensin II (ANG II) may increase blood pressure by central nervous system mechanisms. The involvement of the sympathetic nervous system in the centrally-induced pressor effect of ANG II in the rat was investigated. 2. Plasma noradrenaline concentrations, measured as an index of sympathetic nervous system activity, increased after intracerebroventricular (i.c.v.) injection of pressor doses of ANG II, both in normotensive and in spontaneously hypertensive rts. 3. To assess the functional significance of this, the sympathetic nervous system was inhibited by phentolamine, reserpine, and guanethidine. In phentolamine-infused rats, low doses of i.c.v. ANG II elicited a blood pressure decrease, but at maximal pressor doses, no difference between phentolamine-treated and control rats was observed. In reserpinized rats, the central pressor effect of ANG II was greater than in controls. Guanethidine pretreatment did not affect the blood pressure response to i.c.v. injected ANG II. 4. It is concluded that the central pressor effects of ANG II are accompanied by a stimulation of the sympathetic nervous system. In the rat, this stimulation may be functionally important for the initial phase of the central pressor action. This could not be established for the maximal pressor responses.

Angiotensin II↗
PubMedDate not supplied

Effects of neonatal sympathectomy by 6-hydroxydopamine on blood pressure and intravascular volume in young stroke-prone spontaneously hypertensive rats.

1. Stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were 'chemically sympathectomized' immediately after birth with 6-hydroxydopamine (6-OHDA, 100 mg/kg s.c. daily) for the first 10 days of life. 2. Body weight gain was diminished in both groups as compared with sham-treated controls. Blood pressure was reduced in 'sympathectomized' SHRSP, and also WKY rats had a slightly lower blood pressure than control rats. 3. Plasma concentration of angiotensin II and renin content of the kidney were not influenced by 6-OHDA. 4. 'Sympathectomized' SHRSP retained similar amounts of sodium than sham-treated SHRSP when sodium retention is expressed per body weight gained. Plasma and blood volumes were increased in both SHRSP and WKY rats, whereas packed cell volume was significantly decreased. 5. These results demonstrate the significance of an intact sympathetic nervous system for the development of hypertension in SHRSP. The expanded plasma and blood volume in 'sympathectomized' rats indicate an important role of the sympathetic nervous system and/or the arterial blood pressure for the regulation of intravascular volume.

Angiotensin II↗
PubMedDate not supplied

Central actions and brain receptor binding of angiotensin II: Influence of sodium intake.

The effects of dietary sodium on the central actions of angiotensin II (AII) and on 125I-AII binding to brain membranes were investigated in rats fed a low-sodium or control diet and implanted with a permanent cannula into the lateral cerebral ventricle. Blood pressure (BP) responses to AII injections intracerebroventricularly (i.v.t.) were blunted in sodium-deficient rats compared with controls. The BP increases in response to i.v.t.-injected Carbachol were the same in the two groups. In sodium-depleted rats, water intake was lower than in controls after AII given i.v.t.; higher after 1.5% NaCl i.v.t.; and unchanged after Carbachol i.v.t. The pressor response to AII given i.v.t. was higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) control rats. This hyperresponsiveness to central AII was abolished by feeding a low-sodium diet. Specific 125I-AII binding in vitro to brain membranes was consistently lower in sodium-depleted rats. The results suggest that sodium depletion modifies the central actions of AII. This may be related in part to changes in the binding properties of AII receptors in the brain.

Angiotensin II↗
PubMedDate not supplied

Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.

In stroke-prone spontaneously hypertensive rats (SHRSP) plasma norepinephrine levels and vascular reactivity to norepinephrine are increased and intravascular volume is reduced during the developmental phase of hypertension. Since the accelerated rise in blood pressure following sodium-loading in SHRSP cannot be attributed to the volume-retaining properties of sodium, the effects of an increased dietary intake of sodium on biochemical parameters of sympathetic vascular tone were investigated. The following results were obtained. First, the increased reactivity of vascular smooth muscle was further augmented in sodium-treated SHRSP; the degree of supersensitivity was positively correlated to the plasma sodium concentration. After blockade of the neuronal uptake by 30 microM cocaine, no difference in vascular reactivity to norepinephrine was detected between SHRSP on a normal and SHRSP on a high-sodium diet. Second, the inactivation of norepinephrine by the neuronal uptake was impaired in rats on a high-sodium diet, the impairment being more pronounced in SHRSP than in Wistar-Kyoto (WKY) rats. This decreased inactivation could be expected to cause higher concentrations of the neurotransmitter at the receptor site if the transmitter release from the nerve ending remains constant. Third, the release of norepinephrine and epinephrine into the plasma was increased in sodium-loaded SHRSP but not in sodium-loaded WKY. Cold exposure exaggerates these differences between normotensive and hypertensive rats. These findings suggest that a high-sodium intake modifies the transmission of sympathetic impulses at the level of the nerve terminal in both WKY and SHRSP. In the normotensive rats, moderate impairment of norepinephrine inactivation, however, was balanced by an appropriate reduction in central sympathetic discharge following sodium-loading. In the hypertensive rats, the peripheral disturbance in norepinephrine inactivation due to sodium-loading was obviously not balanced by an adequate withdrawal of central sympathetic discharge. The resultant hemodynamic change was a further increase in the sympathetically mediated vasoconstriction, which is regarded as at least one of the main mechanisms of the sodium-dependent acceleration of hypertension in SHRSP.

Animals↗
PubMedDate not supplied

Development of a new strain of spontaneously hypertensive rats homozygous for hypothalamic diabetes insipidus.

The aim of the present study was to investigate whether the presence of arginine vasopressin (AVP) is necessary for the establishment of high blood pressure in spontaneously hypertensive rats (SHR). For this purpose we crossbred SHR of the stroke-prone substrain (SHRSP) with rats homozygous for hypothalamic diabetes insipidus of the Brattleboro strain (DI) which are unable to synthetize AVP. The successful introduction of the DI gene into the SHRSP strain (SHRDI) was demonstrated by the following observations: In 10-month-old rats, water intake was similarly elevated in SHRDI as in DI rats (137 +/- 6.5 vs 125 +/- 10.5 ml per 24 hours). AVP was undetectable in the plasma, in the hypothalamus, and in the pituitary of SHRDI and DI rats. Urine osmolality and urinary concentration of sodium and potassium were markedly reduced. SHRDI and DI did not adequately concentrate their urine during an 8-hour period of water deprivation, but both strains of rats responded well with a fall in urine output and a rise in urine osmolality to subcutaneous administration of the non-pressor analog of AVP, DDAVP. Mean arterial blood pressure was markedly increased in SHRDI as well as in SHRSP (184 +/- 9.7 vs 197 +/- 5.2 mm Hg). Thus, we have developed a new line of spontaneously hypertensive rats homozygous for hypothalamic diabetes insipidus. From this finding it is concluded that AVP is not essential for the development and maintenance of spontaneous hypertension of rats.

Animals↗