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Biomedical subjects

A Knorr

Publications and source records attributed to A Knorr.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cardiorenal consequences of dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibition in transgenic rats with an extra renin gene.

The cardiovascular consequences of mixed angiotensin converting enzyme and neutral endopeptidase (ACE/NEP) inhibition with alatriopril/alatrioprilat were compared with the consequences of endopeptidase (NEP) inhibition alone with (S)-thiorphan/ecadotril by determining the acute effects of the compounds on hemodynamic, hormonal, and renal parameters in hypertensive transgenic rats harboring an additional mouse renin gene (TGR(mRen2)27). Infusion of alatrioprilat and (S)-thiorphan in anesthetized TGR decreased blood pressure in a dose-dependent manner, but heart rate remained unchanged. The renal excretion of water, sodium, and cGMP also increased dose-dependently, with nearly the same maximal effects after infusion of (S)-thiorphan and alatrioprilat. At the end of infusion, plasma ANP and cGMP were elevated both after (S)-thiorphan and after alatrioprilat, whereas plasma renin activity increased only after alatrioprilat. The ACE inhibition effect was studied in ganglion-blocked rats receiving a continous infusion of angiotensin I. Alatrioprilat decreased the mean blood pressure dose-dependently, but about 30 times higher concentrations were needed to produce the same effects as the ACE inhibitor captopril. At a dose of 30 mg/kg p.o., ecadotril, the orally active prodrug of (S)-thiorphan, decreased the systolic blood pressure in conscious TGR by 22 mmHg for 6 h, whereas alatriopril (100 mg/kg p.o.) also reduced the systolic pressure in these rats with a maximal reduction of 22 mmHg. In addition, ecadotril and alatriopril significantly increased the urinary excretion of sodium. In contrast, ACE inhibition with captopril decreased the excretion of sodium dose-dependently in conscious TGR. In conclusion, combined ACE/NEP inhibition produced a comparable lowering of blood pressure and improvement in renal function as those with NEP inhibition in TGR. Dual ACE/NEP inhibition may therefore be useful in cardiovascular conditions such as hypertension or heart failure.

Alanine↗
PubMed1995

Effects of prazosin on the dopaminergic neurotransmission in rat brain.

Effects of systemic and local administration of prazosin, an alpha 1-adrenoceptor antagonist, on dopaminergic neurotransmission in the caudate putamen and nucleus accumbens were characterized in microdialysis experiments. Prazosin (10 mg/kg s.c.) resulted in blood pressure reduction, however, did not alter dopamine release in the two examined brain areas. In contrast, local administration of prazosin (10 microM) via the microdialysis probe resulted in a clear attenuation of dopamine output, indicating that tonically activated alpha 1-adrenoceptors stimulate dopamine release in the caudate putamen as well as in the nucleus accumbens. The relevance of this finding for antipsychotics exhibiting antagonism at alpha 1-adrenoceptors is discussed.

Animals↗
PubMed1995

Treatment in hypertensive cardiac hypertrophy, I. Neuropeptide Y and beta-adrenoceptors.

In the present study, we investigated serum and myocardial neuropeptide Y concentrations as measures of sympathetic activity as well as myocardial beta-adrenoceptors and beta-adrenoceptor-stimulated adenylyl cyclase activity in spontaneously hypertensive rats (SHR). SHR and control rats at 10 weeks of age were kept on oral treatment with captopril, nitrendipine, or both for 20 weeks. Treatment only slightly reduced but did not normalize blood pressure and cardiac hypertrophy in SHR. The elevated serum concentration of neuropeptide Y, the reduced number of beta-adrenoceptors, and the depressed beta-adrenoceptor-stimulated adenylyl cyclase activity were partly normalized compared with the values observed in control rats. We conclude that antihypertensive treatment, at doses that failed to normalize systolic pressure and to reverse cardiac hypertrophy completely, is able to reduce sympathetic activity in SHR, thereby resensitizing the depressed beta-adrenoceptor-adenylyl cyclase system.

Adenylyl Cyclases↗
PubMed1995

Treatment in hypertensive cardiac hypertrophy, II. Postreceptor events.

We investigated the effect of pharmacological treatment with captopril, nitrendipine, and captopril plus nitrendipine on myocardial heterologous adenylyl cyclase desensitization and the underlying postreceptor defects in spontaneously hypertensive rats (SHR). In myocardial membranes from SHR, stimulation of adenylyl cyclase with guanylylimido-diphosphate (P < .001) and forskolin (P < .05) was significantly reduced, whereas no difference with forskolin was obtained in the presence of manganese chloride. Reconstitution of Gs alpha into Gs alpha-deficient S49 cyc- mouse lymphoma cells revealed no difference between SHR and control rats. In contrast, pertussis toxin labeling of Gi alpha was significantly increased in SHR. The reduction of adenylyl cyclase in SHR was abolished after pertussis toxin treatment of membranes. Treatment with captopril, nitrendipine, or both reduced Gi alpha and increased guanylylimidodiphosphate-stimulated adenylyl cyclase activity in SHR. In summary, heterologous adenylyl cyclase desensitization due to an increase of Gi alpha but in the presence of an unchanged activity of Gs alpha or the catalyst occurs in SHR. This alteration, which could contribute to the progression of contractile dysfunction by producing adrenergic subsensitivity, is sensitive to pharmacological treatment most likely because of a reduction of sympathetic activity.

Adenosine Diphosphate Ribose↗
PubMed1995

Prolonged inhibition of neutral endopeptidase 24.11 by sinorphan in stroke-prone spontaneously hypertensive rats.

The cardiovascular consequences of inhibition of the neutral endopeptidase 24.11 (NEP) with the orally active NEP inhibitor sinorphan were evaluated by determining long-term effects of the drug on hemodynamic, hormonal and structural parameters in stroke-prone spontaneously hypertensive rats (SHR-SP). Systolic blood pressure increased in young SHR-SP from 194 +/- 2 to 266 +/- 7 mmHg, whereas in sinorphan (30 mg/kg p.o. bid) treated animals systolic blood pressure increased only from 193 +/- 4 to 229 +/- 4 mmHg during the treatment period of 9 weeks. The increase in relative heart weight was also delayed. Plasma ANP was higher in the sinorphan group than in the controls. The results of a second study demonstrate a substantial improvement of cardiac pump function and ventricular hypertrophy in old SHR-SP with compromised cardiac function by long-term inhibition of NEP. Thirteen-month-old SHR-SP were treated with sinorphan (30 mg/kg p.o. bid) for two weeks. At the end of experiment, the increase in ANP plasma levels did not reach statistical significance, whereas plasma cGMP was higher in sinorphan treated animals than in controls. Left ventricular end-diastolic pressure was markedly elevated in controls and significantly lower in sinorphan treated animals. In addition, sinorphan reduced cardiac hypertrophy in these old SHR-SP. In conclusion, the results of the present studies demonstrate that long-term NEP inhibition with sinorphan has inhibitory effects on malignant hypertension and associated cardiac hypertrophy in young SHR-SP on a high-sodium diet. NEP inhibition substantially improves cardiac pump function and reduces ventricular hypertrophy of old SHR-SP with compromised cardiac function.

Animals↗
PubMed1995

[Radiogenic lung reactions. Pathogenesis--prevention--therapy].

PURPOSE: The lung is the dose-limiting structure within the thorax. Radiation-induced lung damage resulting in either pneumonitis or pulmonary fibrosis limits the total dose of radiotherapy in the thoracic region. The paper reviewed and discussed the current knowledge of radiogenic pneumopathy. PATIENTS AND METHODS: Analysis was done of experimental results and published data concerning lung reaction after radiotherapy. RESULTS: From a clinical point of view the radiation-induced lung damage can be described by 2 distinct phases: pneumonitis (4 to 6 weeks post radiationem) and pulmonary fibrosis (1 to 2 years post radiationem). Although there is increasing additional information on the etiology of radiation-induced lung damage up to now effective treatment based on these knowledges is available. The frequency of radiogenic pneumopathy detected by X-ray investigation after a radiation treatment demonstrates great difference between several investigators which is mainly caused by differences in the sequence of X-ray investigation. The ED50-value of pneumonitis after a conventional fractionated radiotherapy is about 35 Gy. CONCLUSION: Minimizing the frequency of radiation-induced lung injury it ist necessary to check prior to radiotherapy the treatment ability of a patient concerning its lung function conditions, to remain a great untreated lung volume in treatment planning, to use smaller doses per fraction in the irradiated parts of the lung and to calculate the dose-distribution with the individual values of lung density of the patient. In cases of occurring pneumopathy with clinical signs only symptomatic treatment is possible.

Dose-Response Relationship, Radiation↗
PubMed1994

Crossed fused renal ectopy in children with myelodysplasia.

The medical records of 151 patients with myelodysplasia ranging in age from 3 months to 22 years were reviewed to determine the incidence of crossed fused renal ectopy. Five patients (3.3%) were identified. This figure is considerably higher than the reported incidence of 1:200 (0.5%) to 1:7500 (0.013%) in the general population.

Adolescent↗
PubMed1994

Functional significance of angiotensin receptors in human myocardium. Significant differences between atrial and ventricular myocardium.

We studied the effects of angiotensin (Ang) I and II in a variety of isolated human cardiac tissues contracting under physiological conditions (37 degrees C, 60 beats.min-1). Ang I and II consistently increased the peak developed force of human atrial muscles by 30-40%, an effect that was completely blocked by 10(-6) M saralasine, but not by the combination of prazosin and propranolol. However, neither Ang I or II had significant inotropic effects in right and left ventricular human preparations. We were also able to demonstrate that the positive inotropic effect of Ang II in human right atrial tissue is mediated by the AT1 receptor subtype but not the AT2 receptor subtype.

Angiotensin I↗