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Biomedical subjects

J Holtz

Publications and source records attributed to J Holtz.

154 records · Page 9Linked to original sources
PubMedDate not supplied

Enhanced cardiac angiotensinogen gene expression and angiotensin converting enzyme activity in tachypacing-induced heart failure in rats.

The aim of the study was to analyze changes in myocardial angiotensinogen gene expression and myocardial angiotensin converting enzyme activity in slowly progressing low-output failure. In adult, male Wistar rats, acute ventricular tachypacing by 610 to 620 impulses per minute lowered end-diastolic external diameter of the left ventricle by 2.6% (p less than 0.01), but did not lower cardiac output or abolish coronary reserve, since left-ventricular subendocardial blood flow of paced rats increased under dipyridamole (2 mg/kg i.v.) by 56% (p less than 0.01). Systemic neuroendocrine activation and ventricular dilation without enlargement of ventricular mass developed subsequent to chronic tachypacing, but left-ventricular diameter during pacing never exceeded the value of sham rats on sinus rhythm. After 2 weeks, cardiac output was lowered by 14% (p less than 0.001), cardiopulmonary blood volume was elevated by 30% (p less than 0.001), and angiotensinogen mRNA and angiotensin converting enzyme activity in ventricular myocardium were doubled. We conclude that conditions for an enhanced intracardiac angiotensin II-formation developed in tachypacing-induced heart failure, but that enhanced systolic wall stress or myocardial ischemia are not required for this activation of the local cardiac renin-angiotensin system.

Angiotensinogen↗
PubMedDate not supplied

Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade.

We tested whether the alpha 1- and alpha 2-blocking agent phentolamine can be used to assess the contribution of alpha-adrenergic constriction in circulatory control. In 15 conscious dogs at rest, phentolamine (2 mg/kg i.v.) caused hypotension (-17 mm Hg mean arterial pressure), vasodilation (-29% total peripheral resistance), tachycardia, and an increase in cardiac output, oxygen consumption, and plasma catecholamines. Following beta-adrenoceptor blockade (2 mg/kg i.v. nadolol), phentolamine still produced hypotension and increased plasma catecholamine levels, but neither vasodilation nor augmented oxygen consumption. During beta-blockade, phentolamine caused a 28-fold decrease in the vasoconstrictor response to norepinephrine infusions. An equihypotensive dosage of the alpha 1-adrenoceptor blocking agent prazosin (1.2 mg/kg i.v.) did not elevate heart rate, cardiac output, plasma catecholamines, or oxygen consumption. The prazosin-induced vasodilation was not attenuated by prior beta-blockade, in contrast to the phentolamine-induced vasodilation. It is concluded that phentolamine increased catecholamine release by presynaptic alpha 2-blockade, thereby suppressing the autoinhibition of transmitter release. This excess of catecholamines causes a rise of oxygen consumption and vasodilation by beta-adrenergic stimulation. Under beta-blockade, this excess competitively counteracts the postsynaptic vascular alpha-blockade. The combination of pre- and postsynaptic effects invalidates the use of phentolamine in the assessment of alpha-adrenoceptor-mediated vasoconstrictor tone.

Animals↗
PubMedDate not supplied

Beta-adrenergic activation of the renin-angiotensin system following alpha 2-, alpha 1-, or nonselective alpha-blockade in conscious dogs: no relation to the changes in blood pressure.

We analyzed the role of the renin-angiotensin system following alpha 2-, alpha 1-, or nonselective alpha-blockade in an intact organism in which both postsynaptic alpha-adrenoceptor types contribute to adrenergic vasoconstriction. In conscious dogs, alpha 2-blockade (0.3 mg/kg rauwolscine, n = 10) increased mean arterial pressure by 40 mm Hg, while hypotension by 8 mm Hg occurred following nonselective alpha-blockade (1.5 mg/kg phentolamine, n = 9) and by 20 mm Hg following alpha 1-blockade (1.2 mg/kg prazosin, n = 10). Plasma angiotensin II (pg/ml) rose by 103 +/- 28 (SEM), 143 +/- 48, and 58 +/- 15 following alpha 2-, nonselective alpha-, or alpha 1-blockade, respectively. While alpha 2- or nonselective alpha-blockade induced tachycardia and substantial elevations of plasma catecholamines, alpha 1-blockade did not. Beta-Blockade (2 mg/kg nadolol) attenuated the elevations of angiotensin following alpha 2- or nonselective alpha-blockade by 100 and 88%, respectively, without affecting the alpha 1-blockade-induced elevation, which is mainly mediated by the hypotension. Pretreatment with 3 mg/kg captopril reduced the pressure increase induced by alpha 2-blockade from 40 to 13 +/- 10 mm Hg and aggravated the decline in blood pressure induced by nonselective alpha-blockade from 8 to greater than 50 mm Hg. In anesthetized, spinalized dogs, both types of alpha-blockade competitively antagonized the pressor effect of the alpha 2-agonist azepexole by the same degree. It is concluded that, in the intact animal, the central and peripheral presynaptic augmentation of sympathoexcitation induced by alpha 2- or nonselective alpha-blockade leads to a strong beta-adrenergic activation of the renin-angiotensin system, independent of the concomitant changes in blood pressure. The constrictive action of the activation contributes substantially to the compensation of the vascular adrenoceptor blockade induced by nonselective or alpha 2-selective blockade in the intact organism.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Sympathetic control of myocardial oxygen balance in dogs mediated by activation of coronary vascular alpha 2-adrenoceptors.

Recent observations on sympathetic constriction of the poststenotic coronary bed without dilatory reserve indicate the involvement of postsynaptic alpha 2-adrenoceptors, which are commonly regarded as noninnervated, hormonal receptors. Therefore, we characterized the vascular alpha-adrenoceptor activated during the competition between sympathetic constriction and metabolic dilation of the nonstenosed coronary bed by analyzing myocardial oxygen balance. In 39 anesthetized, spinalized open-chest dogs with bilateral cervical vagotomy, the left decentralized stellate ganglion was stimulated while mean aortic pressure was kept constant. Stimulation at 1 and 10 Hz lowered coronary venous oxygen saturation by 2.5 +/- 0.3 (SEM) and by 11.1 +/- 0.8 saturation %, respectively, in experiments under beta-blockade (4 mg/kg nadolol, n = 21). In experiments without beta-blockade (n = 18), the saturation response was similar. Under beta-blockade, alpha 2-blockade by rauwolscine (0.03 and 0.3 mg/kg) attenuated the decline in saturation induced by 10 Hz stimulation to 0.56 +/- 0.08 (p less than 0.01) of the control response and to 0.30 +/- 0.06 (p less than 0.001), respectively, whereas alpha 1-blockade by prazosin (0.012 and 0.12 mg/kg) modified this response only to 0.94 +/- 0.06 (NS) and to 0.75 +/- 0.08 (0.1 greater than p greater than 0.05). Without beta-blockade, similar attenuations to 0.36 +/- 0.07 (p less than 0.001) by 0.3 mg/kg rauwolscine and to 0.80 +/- 0.09 (NS) by 0.12 mg/kg prazosin were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Endothelium-mediated dilations contribute to the polarity of the arterial wall in vasomotion induced by alpha 2-adrenergic agonists.

We tested whether or not an endothelium-mediated dilation is involved in the response of intact arteries to alpha-adrenergic stimulation, by separately applying agonists to the luminal or adventitial side of the arterial wall. Cumulative dose-response curves of the alpha 1-agonists l-phenylephrine or cirazoline applied luminally in rat tail arteries and in side branches of canine femoral arteries were identical to those obtained by adventitial application in the intact arteries, and were not modified by removal of the endothelium (eliminating acetylcholine-induced dilations). Constrictions induced by the alpha 2-agonists UK-14,304 or azepexole applied luminally were significantly lower than those induced by adventitial application, and were augmented significantly by removal of the endothelium. Half-maximally precontracted arteries were dilated by addition of alpha 2-agonists to the luminal perfusate; these dilations were abolished by removal of the endothelium. It is concluded that the functional polarity of the vascular wall of these arteries in response to alpha 2-agonists results from the release of a dilatory signal from the endothelial cells, counteracting the direct contractile activation of the adjacent smooth muscle cells by the agonists.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Sympathetic vasoconstriction sensitive to alpha 2-adrenergic receptor blockade. No evidence for preferential innervation of alpha 1-adrenergic receptors in the canine femoral bed.

In the canine femoral bed, we studied the involvement of vascular alpha 2-adrenergic receptors in vasoconstriction by stimulating the sympathetic nerve during different degrees of activation of metabolic counterregulation (constant pressure and constant flow perfusion). In chloralose-anesthetized, despinalized dogs under beta-blockade (2 mg/kg nadolol) and under a constant femoral perfusion pressure, cumulative doses of rauwolscine (0.03, 0.3, and 3.0 mg/kg i.v., n = 8) or of prazosin (0.012, 0.12, and 1.2 mg/kg i.v., n = 8) caused dose-dependent shifts to the right of the dose-response curve of intraarterial norepinephrine (NE) infusions. These cumulative doses also caused attenuations of the vasoconstriction initiated by lumbar sympathetic stimulation (0.1, 0.3, 1.0, and 3.0 Hz). Sham treatment (n = 8) had no such results. In experiments with constant flow perfusion (n = 6 for each antagonist), rauwolscine shifted the NE dose-response curve significantly more compared to the experiments with constant pressure perfusion, while prazosin was similarly effective under both conditions. Under constant flow perfusion, both antagonists dose-dependently attenuated the vasoconstrictions caused by sympathetic stimulation. While prazosin and sham treatment did not modify the overflow of NE from the femoral bed during stimulation, this overflow was augmented by rauwolscine during stimulation at 3 Hz, which indicated presynaptic modulation of NE release. Under both experimental conditions, no significant difference could be observed in the attenuation of low-frequency sympathetic vasoconstriction by the two antagonists, when dosages were compared on the basis of their action against infused NE. It is concluded that both a rauwolscine-sensitive component and a prazosin-sensitive component are involved in the competition between sympathetic vasoconstriction and metabolic dilation. The vascular alpha-adrenergic receptors activated by these two components have a similar postsynaptic localization relative to the nerve endings.

Animals↗
PubMedDate not supplied

[Development of operative therapy in a public hospital 1910 to 1980].

An analysis of the operation records for the years from 1910 to 1980 shows a considerable increase in the indication for surgical treatment. While the average age of the groups of patients does not increase in general, an increase in the number of patients operated on in higher age can be proved. This paper gives an outline of problems of preparation for operations, the application of narcosis techniques and postoperational care for these groups of patients.

Adolescent↗
PubMedDate not supplied

Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition.

Endothelial damage or removal abolishes the dilation of epicardial coronary arteries induced by increments in flow through these arteries in vitro. Therefore, we tested whether or not the release of a cyclooxygenase product from endothelial cells in vivo is the mechanism of this flow-dependent dilation. In eight conscious dogs, instrumented to register the external diameter of two epicardial branches--anterior descending and circumflex--of the left coronary artery, increments in coronary flow increased and reductions in coronary flow decreased the diameter of the left circumflex epicardial artery by 182 +/- 11 micron/100% change in flow. When mean coronary flow in one epicardial branch was kept constant by a distal, flow-limiting stenosis during the application of flow-augmenting stimuli (temporal coronary occlusion or 80-400 micrograms/kg adenosine i.v.), no dilation of this artery was observed. Cyclooxygenase inhibition (suppressing the bradykinin-induced elevation of plasma 6-keto-PGF1 alpha) by indomethacin (5 mg/kg) or by diclofenac (10 mg/kg) increased smooth muscle tone in both epicardial arteries, but did not modify the flow-diameter relation (181 +/- 10 and 179 +/- 9 microns/100% change in flow, respectively). It is concluded that a tonic, instantaneous influence of coronary flow on the smooth muscle tone of the epicardial coronary arteries exists in vivo. It is unlikely that prostacyclin or another prostanoid is a mediator of this endothelium-mediated influence of flow on smooth muscle tone.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

[Applications of polymerase chain reaction in identifying the D1S80 (pMCT 118) locus in forensic DNA analysis].

The value of the amplified fragment length polymorphism at the D1S80 locus was examples by means of examples of forensic casework (paternity and identification cases). Parameters, like PCR conditions, limit of detection and analysis of mixed samples are discussed. In a population study the allele and genotype frequencies of 154 individuals from the area of Bonn were determined. The distribution of genotypes was in agreement with expected values according to the Hardy-Weinberg equilibrium. There was no deviation from other published Middle European studies.

Alleles↗