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M Pohl

Publications and source records attributed to M Pohl.

At least 109 records · Page 6Linked to original sources

Angiotensin II-like material extracted from the rat brain is distinct from authentic angiotensin II.

Specific radioimmunoassay and radioreceptor assay for angiotensin II (A II) were used for the possible identification of this peptide in the rat brain. An A II-like material (A II-LM) was detected with both assays applied to acidic extracts of various brain structures. The regional distribution of A II-LM was uneven, but absolute levels (in A II equivalents) could not be accurately determined, as they were highly dependent on the assay used. Partial purification of A II-LM by Sep-Pak C 18 chromatography and affinity chromatography using anti-A II antibodies bound to Ultrogel gave a compound coeluting with authentic A II in reverse-phase HPLC. However, gel filtration through Sephadex G-25 and TSK Spherogel 3000 SW as well as anion exchange HPLC demonstrated that A II-LM did not correspond to authentic A II. Partial characterization of A II-LM indicated that this compound was probably a peptide with an apparent molecular weight of 5,000-7,000 (instead of 1,046 for A II) and more polar but less positively charged than A II. Whether A II-LM is, in fact, the endogenous ligand of A II binding sites in brain remains an interesting hypothesis for further investigations.

Angiotensin II↗

Clinical implications of primary aldosteronism with resistant hypertension.

Twenty-eight patients with resistant hypertension were found to have primary aldosteronism; 25 had solitary adenoma and 3 had adrenal hyperplasia. All were severely hypertensive despite receiving three or more antihypertensive agents, including conventional doses of diuretics, sympatholytics, and vasodilators. Hypervolemia (24 patients) or normovolemia (2 patients) despite severe diastolic hypertension was the hallmark in 26 patients. Adequate salt and water depletion alone with spironolactone (200 mg/day) and hydrochlorothiazide (50-100 ng/day) reduced arterial pressure in all. Twenty-two patients had surgical removal of a solitary adenoma. Over 1 to 2 years of follow-up, 13 were normotensive without medication, and six required hydrochlorothiazide and three hydrochlorothiazide plus a beta-blocker to normalize blood pressure. Blood pressure response to surgery had no relation to either duration or severity of hypertension. Six patients (three with hyperplasia, three with adenoma) have continued diuretic therapy and are normokalemic and normotensive. These results indicate that primary aldosteronism can be associated with sever and drug-resistant hypertension, that maintained hypervolemia is the reason for resistance to therapy, that sustained volume depletion is the most important therapeutic goal for these patients, and that cure can be achieved despite prolonged and severe hypertension.

Adenoma↗

Anti-metrazol action of R 57720 during postnatal development in rats.

The effects of an experimental antiepileptic drug R 57720 (Janssen Pharmaceutica) on metrazol-induced seizures were studied in rats aged 7, 12, 18, 25 and 90 days. R 57720 exhibited a marked dose-dependent anticonvulsant effect against major, generalized tonic-clonic seizures in all the age groups studied. Similar action on minimal metrazol seizures (mMS) was present in rats aged 18 days and more. In the two youngest groups where metrazol did not induce mMS under control conditions, the combination of the 5- and 10-mg/kg doses of R 57720 and metrazol led to the appearance of mMS, whereas mMS failed to appear after the highest dose of R 57720 used (20 mg/kg).

Aging↗

Effects of flunarizine on Metrazol-induced seizures in developing rats.

Antimetrazol action of flunarizine (5, 10, 20 and 40 mg/kg i.p.) was tested during ontogenesis on male Wistar rats aged 7, 12, 18, 25 and 90 days. The latencies and incidences of jerks, minimal Metrazol seizures and major Metrazol seizures remained unchanged by flunarizine in all age groups. A specific action (an abolition of the tonic phase of major seizures) was seen throughout the development and was reflected in lower scores of seizures.

Aging↗

Bronchosparing properties of celiprolol, a new beta 1, alpha 2-blocker, in propranolol-sensitive asthmatic patients.

The bronchopulmonary effects of celiprolol were studied in 12 male asthmatic patients who showed mean maximum changes of -24% in forced one-second expiratory volume (FEV1) and 130% in airways resistance (Raw) following a single, 80 mg dose of propranolol. Celiprolol 200 and 400 mg and placebo were administered in double-blind, random fashion. Raw and FEV1 were determined by whole body plethysmography 1, 2, and 3 h post dose. For placebo and celiprolol 200 and 400 mg, mean maximum changes in FEV1 were 0.6, 2.8, and 2.4%, and for Raw, 11.3, -0.2, and -10.9%, respectively. Pulmonary effects of the three treatments were indistinguishable but differed significantly from propranolol. Five 0.5 mg doses of terbutaline aerosol, administered at 15-min intervals starting 3 h post drug or placebo, caused less bronchodilation after propranolol than after placebo, or celiprolol 200 or 400 mg; the responses after the latter three were indistinguishable. These results suggest that celiprolol is highly bronchosparing and does not block bronchodilation following the beta 2-agonist terbutaline in propranolol-sensitive asthmatics. In contrast to classical beta-adrenoceptor antagonists, celiprolol may afford a greater margin of safety in asthmatic patients with angina or hypertension.

Adrenergic alpha-Antagonists↗

Rhythmic metrazol activity and cortical spreading depression.

The incidence of segments of rhythmic metrazol activity (RMA) in cortical leads and in the thalamus and hippocampus was studied in acute experiments on nine male albino laboratory rats. First of all we studied activity after administering metrazol in an i.p. dose of 50 mg/kg, without any further treatment, and then, after a control recording, we induced cortical spreading depression and observed its effect on the incidence and synchronization of RMA in the individual leads. We came to the conclusion that the thalamus is incapable of isolated production of RMA. The cortex is able to produce RMA without participation by the studied structures of the specific thalamus and hippocampus; RMA probably originates in the cortex itself. Generalization is impaired, but not eliminated, by a cortical block. The hippocampus independently produces another type of rhythmic activity.

Animals↗

Partial characterization of angiotensin II-like material extracted from the rat brain.

Angiotensin II (ANG II)-like material was detected in acid extracts of rat brain using radio-immunoassay (RIA) and a radioreceptor assay (RRA). This material, expressed as ANG II equivalents, corresponded to 131 +/- 20 fmol/g and 33 +/- 4 pmol/g as assessed by RIA and RRA respectively. Such quantitative differences indicated that the brain material did not behave as authentic ANG II in both assays, and further chromatographic investigations confirmed this inference. In particular, gel filtration through Sephadex G-25 and TSK Spherogel 3000 SW revealed that the apparent molecular weight of ANG II-like material was much higher (approximately 5000-7000) than that of authentic ANG II. Furthermore, in contrast to the marked hypertension due to ANG II, a decrease in blood pressure (BP) was observed in rats following the systemic administration of chromatographic eluates enriched with brain ANG II-like material.

Angiotensin II↗

Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease.

We studied renal plasma flow and glomerular filtration rate during graded blood pressure reduction induced with sodium nitroprusside infusion in 16 hypertensive patients with atherosclerotic renovascular disease. Eight patients with unilateral disease tolerated pressure reduction from 205 +/- 9 (SE)/103 +/- 2 mm Hg to 146 +/- 6/84 +/- 3 mm Hg (p less than 0.01) with no change in total renal function. In 8 other patients with bilateral renal arterial stenosis (all arteries 70% or more stenosed), similar pressure reduction produced marked but reversible decrements in plasma flow (152 +/- 28 mL/min to 66 +/- 13 mL/min; p less than 0.01) and glomerular filtration rate (38 +/- 8 mL/min to 16 +/- mL/min; p less than 0.01). In 4 patients restudied after revascularization, sensitivity of renal function to pressure changes was no longer present. These data indicate that vascular stenosis to the entire renal mass may limit function and provide a means for evaluating patients at risk for loss of renal function during antihypertensive therapy.

Aged↗

Effect of anticonvulsant drugs on thalamo-cortical and hippocampo-cortical self-sustained after-discharges in the rat.

The action of four antiepileptic drugs was studied in acute experiments in 98 rats. Two types of cortical self-sustained afterdischarges ( SSADs ) induced by rhythmic electrical stimulation of subcortical structures were used as models. SSAD formed by the spike-and-wave rhythm (most frequently induced by stimulation of thalamic somatosensory relay nucleus) was almost completely blocked by dipropylacetate (valproate, 400 mg/kg i.p.) and significantly shortened by ethosuximide (125 mg/kg i.p.). Diphenylhydantoin (60 mg/kg i.p.) tended to prolong this type of SSAD whereas carbamazepine did not influence it. SSAD formed by serrated waves (induced usually by stimulation of the dorsal hippocampus) was augmented by ethosuximide, uninfluenced by dipropylacetate and diphenylhydantoin, and significantly shortened by carbamazepine. The pharmacological profile of the two types of SSADs is in agreement with our hypothesis that the spike-and-wave type of SSAD represents a model of primary generalized seizures of the absence type whereas hippocampo -cortical SSAD could be used as a model of partial seizures with complex symptomatology.

Animals↗

Localization of the origin of metrazol-induced rhythmic electrocorticographic activity in rats.

In acute experiments we studied the structures essential for the genesis of rhythmic electrocorticographic activity composed of spike-and-wave rhythm of 5 Hz frequency evoked in rats by the systemic administration of pentamethylenetetrazol. Brain stem transection at intercollicular level did not prevent this rhythmic activity from developing. Episodes of this activity were suppressed during a wave of thalamic spreading depression--in every case on the side of depression and in more than half the cases also in the contralateral hemisphere. We further observed that the effect on rhythmic activity in the sensorimotor and visual region was unequal. It can be concluded that the thalamocortical system is essential for the development of rhythmic metrazol spike-and-wave activity, but that this system is not functionally homogeneous.

Animals↗

Reversible blockade of cardiac efferents with procaine instilled into the pericardium of cats.

The blocking of afferent signals from the heart by the instillation of local anaesthetics into the pericardium has frequently been used for studying cardiac reflexes. Yet no attempts have been made to define what effects this has on efferent cardiac drive. Therefore, in nine chloralosed cats with open chests and catheters sewn into the pericardium the procaine concentrations were determined which would block the heart rate responses to electrostimulation of the vagi nerves or the stellate ganglia. The procaine effects on arterial pressure and left ventricular peak positive dP/dt were also evaluated and in 11 cats the vagolytic effects of atropine (0.25 mg . kg-1, intravenous) and intrapericardial procaine (0.1%) were compared. As little as 0.05% procaine attenuated the bradycardia associated with stimulation of the stellate ganglia by only about 30%. Virtual elimination of both sympathetic and vagal drive was achieved with 0.5% procaine having only mild effects on blood pressure and left ventricular dP/dt. Atropine (0.25 mg . kg-1, intravenously) and procaine (0.1% intrapericardially) affected heart rate equally. With procaine in the pericardium it is possible to reversibly and selectively block cardiac efferents and to separate vagal and sympathetic drive by choosing the appropriate concentration of the local anaesthetic.

Animals↗

Synchronization of double asymmetrical epileptogenic foci in the cerebral cortex of the rat.

Discharges of two asymmetrical penicillin foci progressively synchronized during 25 min after creation of these foci. Section of the corpus callosum seriously impaired but did not completely block this synchronization. Thalamic spreading depression did not significantly change the synchronization in rats with intact corpus callosum. Noncallosal component of synchronization is probably realized through brain stem structures.

Animals↗