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Biomedical subjects

A Sastre

Publications and source records attributed to A Sastre.

At least 73 records · Page 4Linked to original sources
PubMed1984

Regional differences in alpha 1-adrenoceptor numbers and responses in canine aorta.

The relationship between active force and alpha 1-adrenergic receptor binding in vascular smooth muscle was measured on strips of canine aorta. After measurement of the isometric force produced by l-phenylephrine and l-norepinephrine in vitro, [3H]prazosin was used to determine the affinity and numbers of alpha 1-receptors in homogenates prepared from the strips. Maximum active stress was 440 g/cm2 in the ascending, 317 in the descending thoracic, and 252 in the abdominal aorta. The total number of alpha 1-receptors per gram arterial wall averaged 576, 237, and 136 fmol/g, respectively. Affinity of the receptors was the same in all regions for prazosin (87 pM) and l-phenylephrine (9 microM). The relation between number of agonist-occupied receptors and response was similar in all regions but nonlinear; 50% of the maximum stress developed when only 2-11% of the receptors were occupied. Differences of contractile response within the vascular tree may thus arise from regional differences in the number of appropriate receptors present, rather than differences of affinity or occupation-response relationships.

Animals↗
PubMed1984

Serum angiotensin-converting enzyme in severe nonthyroidal illnesses associated with low serum thyroxine concentration.

We evaluated serum angiotensin-converting enzyme levels as an index of thyroid hormone action in severe systemic illness. Angiotensin-converting enzyme was elevated in hyperthyroid patients (37.3 +/- 3.2 U/mL, p less than 0.01) and depressed in hypothyroid patients (17.9 +/- 1.4 U/mL, p less than 0.05). Compared with normal controls (22.6 +/- 1.6 U/mL), patients in an intensive care unit with free thyroxine index greater than 5.0 had normal angiotensin-converting enzyme levels (19.1 +/- 2.5 U/mL), but patients with a free thyroxine index less than 5.0 had angiotensin-converting enzyme levels significantly lower than the normal and hypothyroid groups (10.7 +/- 1.0 U/mL, p less than 0.05). A group of patients in an intensive care unit with alcoholic liver disease (known to elevate angiotensin-converting enzyme) and a low free thyroxine index had depressed angiotensin-converting enzyme levels (16.9 +/- 1.5 U/mL, p less than 0.01). A strong correlation was seen in the combined groups of all patients studied between levels of angiotensin-converting enzyme and a free thyroxine index (r = 0.70, p less than 0.01) and free T3 index (r = 0.72, p less than 0.01).

Critical Care↗
PubMed1984

Relation between alpha adrenergic receptor occupation and contractile response: radioligand and physiologic studies in canine aorta.

The relation between occupation of alpha-1 adrenergic receptors by an agonist and the resulting force was examined in the canine aorta in vitro. Methods of preparing membrane preparations for radioligand studies were improved to maximize the yield of receptors from strips of aortic wall. [3H]Prazosin was a reliable ligand, binding to a single class of receptors with a dissociation constant of 97 (+/- 10) pM. Agonists and antagonists displaced [3H]prazosin in a manner consistent with binding to a single class of sites, with Hill coefficients near unity. The rank order of drug potencies determined by competition with [3H]prazosin was characteristic of alpha adrenergic receptors of the alpha-1 subtype. Conventional measurements of maximum isometric force and dose-response relations for l-phenylephrine in strips of ascending aorta in vitro were followed by radioligand studies on homogenates made from the same strips. The number of receptors was 38.8 (+/- 2.9) fmol/mg of protein in the homogenate, corresponding to 580 (+/- 41) fmol/g of aortic wall, a value at least twice as high as any reported previously. Maximum active stress was 440 (+/- 23) g/cm2. Concentration-response curves to l-phenylephrine were relatively shallow, with a Hill coefficient of 0.63 and an ED50 of 1.1 (+/- 0.24) microM. The curve relating receptor occupation to response (force development) in the ascending aorta was consequently nonlinear; 50% of the maximum response occurred when only 10% of the receptors were occupied. Occupation of virtually all receptors (greater than or equal to 97%) was required to produce maximum response, suggesting an absence of "spare" receptors.

Animals↗
PubMed1983

Obligatory role of a Tris/choline allosteric site in guanine nucleotide regulation of [3H]-L-QNB binding to muscarinic acetylcholine receptors.

Tris and choline reduce the maximal binding capacity (RT) of the muscarinic cholinergic antagonist [3H]-L-quinuclidinyl benzilate ([3H]-L-QNB) to atrial membranes, when compared to control values in physiological salt solution (PBS) or NaPi buffer. Addition of guanine nucleotides (GN) to incubations containing choline or Tris reverses the effect of choline and Tris on RT and restores it to levels determined in NaPi or PBS alone. GN addition fails to alter RT or KD values determined in NaPi or PBS in the absence of choline and Tris. This GN effect follows a nucleotide specificity similar to that of the GN regulatory proteins coupled to adenylate cyclase. Tris or choline are required for the expression of GN regulation of [3H]-L-QNB binding to muscarinic acetylcholine receptors (mAChR). An allosteric site recognizing choline and Tris appears involved in the interaction between the guanine nucleotide regulatory protein and antagonist binding to mAChR.

Animals↗
PubMed1983

Clinical correlations of serum angiotensin-converting enzyme (ACE) in sarcoidosis. A longitudinal study of serum ACE, 67gallium scans, chest roentgenograms, and pulmonary function.

Thirty-one patients with biopsy-confirmed sarcoidosis were studied for two to four years to compare serum angiotensin-converting enzyme (ACE) levels to clinical status, 67gallium scans, chest x-ray films, and pulmonary function tests (PFTs). Serum ACE levels and changes in ACE level correlated best with the clinical status of patients and their gallium scans (p less than 0.0005), and less with their chest x-ray films (p = 0.012) or PFTs (p = 0.007). The gallium scan was especially useful for localizing areas of disease involvement. Serial measurements of serum ACE were found to be a sensitive means for following the clinical course of patients with sarcoidosis and at times for predicting clinical relapse or improvement.

Adolescent↗
PubMed1983

Angiotensin-converting enzyme activity in postmortem human tissues.

Angiotensin-converting enzyme (ACE) was assayed spectrophotometrically with hippuryl-histidyl-leucine as substrate. Postmortem tissues from 11 patients with various causes of death and pancreatic juice obtained during endoscopic cannulation of the pancreatic duct were assayed. Activity of most human tissues other than those of the gastrointestinal tract were found to be predominantly associated with the particulate fraction of the homogenates. Tissues with more than twice the ACE activity of lung included kidney, ileum, duodenum, and uterus; seven tissues with ACE activity approximately equal to that of lung included prostate, jejunum, lymph node, thyroid, colon, testis, and adrenal. Twelve other tissues had lower levels of activity with the heart consistently showing the least ACE activity. In the small intestine, the level of ACE activity increased with increasing distance from the pylorus. Inhibitors of ACE were detected in most tissues by assaying serial dilutions of the tissue homogenate; the presence of partial inhibitors did not significantly affect the relative activities of the various tissues. Lysis of hippuryl-histidyl-leucine by the pancreas and pancreatic juice resulted from an enzyme believed to be carboxypeptidase A which is present as a zymogen and activated by trypsin; this activity differed from ACE in that it had a smaller molecular weight (25,000) compared with ACE of serum (240,000), and it was not strongly inhibited by ethylenediaminetetraacetic acid or SQ 20881 (a specific ACE inhibitor). These studies show that human tissues vary in their content of ACE and suggest that ACE may serve a digestive or detoxifying role in the human small intestine and kidney, as well as functioning to activate angiotensin I.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Elevation of serum angiotensin-converting enzyme level. Occurrence in alcoholic liver disease.

Serum angiotensin-converting enzyme (ACE) levels were measured in 151 patients with chronic alcoholism and alcoholic liver disease. The mean serum ACE level was elevated to 30.8 +/- 13 units/mL compared with 22.8 +/- 6 units/mL in control subjects. Approximately 30.0% of the patients had elevated ACE levels. Abstinence from alcohol for six to 27 months by 11 patients was associated with persistently normal serum ACE levels. Angiotensin-converting enzyme level elevations did not correlate with abnormalities of other liver function test results or with any acute clinical condition associated with alcoholic cirrhosis. Hypoxemia was not present in the patients with elevated serum ACE levels. Elevations of serum ACE levels in patients with alcoholic liver disease may relate to an effect of alcohol on the hepatic-sinusoidal lining cells. This elevation could interfere with the use of this test for supporting the diagnosis of sarcoidosis.

Alcohol Drinking↗
PubMed1980

Serum angiotensin-converting enzyme: elevations in diabetes mellitus.

Elevated levels of serum angiotensin-converting enzyme were detected in 24% of 265 patients with diabetes mellitus. The elevations correlated strongly with the presence of severe retinopathy. Diabetes mellitus must be considered when an assay of serum angiotensin-converting enzyme is used to confirm a diagnosis of sarcoidosis.

Cardiovascular Diseases↗