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Biomedical subjects

D S Weber

Publications and source records attributed to D S Weber.

At least 19 recordsLinked to original sources
PubMed2001

Angiotensin II AT1 receptors preserve vasodilator reactivity in skeletal muscle resistance arteries.

Resistance arteries (100-150 microm) were isolated from the gracilis muscle of normotensive Sprague-Dawley rats placed on a high-salt (HS) diet (4.0% NaCl) for 3-7 days. Exposure to the HS diet eliminated vascular relaxation in response to hypoxia (PO2 reduction to 35-40 Torr) and iloprost, a stable analog of prostacyclin. Vasodilator responses were restored in arteries isolated from chronically instrumented HS rats receiving a continuous intravenous infusion of either angiotensin II (ANG II; 5-6 ng x kg(-1) x min(-1)) or ANG II plus the AT2 receptor blocker PD-123319 (5 microg x kg(-1) x min(-1)) for 3 days before the isolated vessel studies. In contrast, coinfusion of the AT1 receptor blocker losartan (20 microg x kg(-1) x min(-1)) or coinfusion of both receptor blockers with ANG II eliminated the protective effect of ANG II to restore dilator responses to hypoxia and iloprost. Neither a HS diet nor ANG II infusion affected the dilation of gracilis arteries in response to direct activation of adenylyl cyclase by forskolin, suggesting that the effect of both the HS diet and the ANG II on the vasculature is mediated upstream from second messenger systems. These findings indicate that the protective effect of ANG II to maintain vasodilator reactivity in resistance arteries of rats on a HS diet is mediated via the AT1 receptor subtype.

Angiotensin II↗
PubMed2001

Enhanced relaxation to the rho-kinase inhibitor Y-27632 in mesenteric arteries from mineralocorticoid hypertensive rats.

Increased vasoconstriction is characteristic of hypertension. In this study, we tested the hypothesis that changes in vascular responses during mineralocorticoid hypertension may be due to increased activation of the Rho/Rho-kinase pathway. To test this, relaxation responses to the Rho-kinase inhibitor Y-27632 were determined by measuring isometric force in deendothelialized mesenteric arteries from mineralocorticoid-hypertensive rats and sham-operated controls. Following agonist-induced contraction by serotonin (5-HT, 5-hydroxytryptamine), arteries from hypertensive rats demonstrated a greater relaxation to the Rho-kinase inhibitor Y-27632 (65 +/- 5% vs. 28 +/- 10%). Treatment with an EC50 concentration of Y-27632 following a KCl-induced contraction caused minimal relaxation of arteries in both groups of animals. These findings suggest that augmented Rho-kinase activity in the vasculature of mineralocorticoid hypertensive rats may contribute to the enhanced vascular reactivity of agonist-mediated stimuli characteristic of this model of hypertension.

Amides↗
PubMed2000

An empirical genetic assessment of the severity of the northern elephant seal population bottleneck.

A bottleneck in population size of a species is often correlated with a sharp reduction in genetic variation. The northern elephant seal (Mirounga angustirostris) has undergone at least one extreme bottleneck, having rebounded from 20-100 individuals a century ago to over 175,000 individuals today. The relative lack of molecular-genetic variation in contemporary populations has been documented, but the extent of variation before the late 19th century remains unknown. We have determined the nucleotide sequence of a 179 base-pair segment of the mitochondrial DNA (mtDNA) control region from seals that lived before, during and after a bottleneck low in 1892. A 'primerless' PCR was used to improve the recovery of information from older samples. Only two mtDNA genotypes were present in all 150+ seals from the 1892 bottleneck on, but we discovered four genotypes in five pre-bottleneck seals. This suggests a much greater amount of mtDNA genotypic variation before this bottleneck, and that the persistence of two genotypes today is a consequence of random lineage sampling. We cannot correlate the loss of mtDNA genotypes with a lowered mean fitness of individuals in the species today. However, we show that the species historically possessed additional genotypes to those present now, and that sampling of ancient DNA could elucidate the genetic consequences of severe reductions in population size.

Animals↗
PubMed2000

Elevated salt intake impairs dilation of rat skeletal muscle resistance arteries via ANG II suppression.

Vasodilator responses were assessed in resistance arteries (100-200 microm) isolated from the gracilis muscle of normotensive rats after changes in dietary salt intake. Sprague-Dawley rats were maintained on either a high-salt (HS) diet (4.0% NaCl) or a low-salt (LS) diet (0.4% NaCl) for 4-8 wk (chronic) or 3 days (short-term) with water ad libitum. One group of short-term HS rats received a continuous intravenous infusion of a low dose (5 ng x kg(-1) x min(-1)) of ANG II to prevent the ANG II suppression that occurs with HS diet. Short-term and chronic HS diet eliminated arterial dilation in response to ACh and reduced PO(2) (30-40 mmHg) and the stable prostacyclin analog iloprost. ANG II infusion preserved the response to these vasodilator stimuli in short-term HS animals. Dilator responses to sodium nitroprusside and forskolin were unaffected by HS diet. These findings suggest that ANG II suppression during HS diet impairs vascular relaxation mechanisms upstream from the cAMP and cGMP second messenger systems.

Angiotensin II↗
PubMed1999

Selective potentiation of angiotensin-induced constriction of skeletal muscle resistance arteries by chronic elevations in dietary salt intake.

Sprague-Dawley rats were fed either a high-salt (HS, 4.0% NaCl) or a low-salt (LS, 0.4% NaCl) diet for 3 days (short-term) or 4-8 weeks (chronic). Vasoconstrictor responses to angiotensin II and norepinephrine were determined in isolated skeletal muscle resistance arteries and in distal arterioles of the in situ cremaster muscle. Myogenic responses to increases in transmural pressure were also assessed in skeletal muscle resistance arteries of animals on high- or low-salt diets. Chronic (but not short-term) HS diet selectively potentiated angiotensin II-induced constriction of skeletal muscle resistance arteries relative to vessels from LS controls. Myogenic responses and norepinephrine-induced constriction of resistance arteries were unaffected by either chronic or short-term HS diet. Constriction of cremasteric arterioles in response to angiotensin II and norepinephrine was unaffected by chronic or short-term elevations in dietary salt intake. These data suggest that chronic elevations in dietary salt intake lead to a selective increase in the constriction of skeletal muscle resistance arteries to angiotensin II that may allow these vessels to continue to regulate their tone in response to this peptide, despite the suppression of angiotensin II that occurs with high-salt diet.

Angiotensin II↗
PubMed1999

Chronic captopril administration decreases vasodilator responses in skeletal muscle arterioles.

Changes in arteriolar reactivity to dilator agonists were assessed in the cremaster muscle of Sprague-Dawley rats fed normal rat chow with captopril (100 mg/kg/day) in the drinking water for 8 weeks and in nontreated controls. The in situ cremaster muscle was prepared, superfused with physiologic salt solution, and arteriolar diameter was measured using television microscopy. Changes in the diameter of distal arterioles in response to topical application of iloprost, forskolin, cholera toxin, acetylcholine, and nitroprusside were measured with a video micrometer. Arteriolar responses to each of the vasodilator agonists used in this study were significantly reduced in the captopril-treated rats, relative to the untreated controls. The maximum dilation of the arterioles, determined during superfusion with Ca2+-free physiologic salt solution containing 10(-4) mol/L adenosine, was also reduced in the captopril-treated rats, suggesting structural remodeling of the arteriolar wall. These observations indicate that chronic angiotensin converting enzyme inhibition with captopril leads to significant alterations in arteriolar structure and reactivity, and that angiotensin II may play a protective role in maintaining normal vascular structure and vasodilator reactivity in the microcirculation.

Acetylcholine↗
PubMed1993

The application of NMR-pattern-recognition methods to the classification of reduced, peracetylated oligosaccharide residues.

In the present paper homo- and hetero-nuclear correlation spectroscopies have been used to assign proton and carbonyl carbon resonances of a number of reduced, peracetylated mono- and oligo-saccharide derivatives. Each of the native structures for which assignments were made represent residues or substructures typically found in N- or O-linked glycans. Using the assigned NMR parameters as a basis, residues contained in parent structures were classified according to their residue type and glycosidic substitution sites using a relatively simple K-Nearest Neighbor pattern recognition approach. The method was able to correctly assign 99% of 77 "test residues" to their correct structural class using the full set of 19 assigned parameters as a basis. Similar correlations made between data and structure were less successful when reduced variable sets selected on the basis of SIMCA optimization were used.

Acetylation↗
PubMed1992

A convenient method for the preparation of a variety of 13C-substituted D-fructose phosphates using readily available enzymes of the glycolytic pathway.

Methods are presented for the preparation of a variety of D-fructose phosphates, 13C-substituted at any single carbon site or at any two symmetrically disposed carbon sites, from either 13C-substituted pyruvate or L-alanine. It is demonstrated that millimole quantities of product can be obtained in good yield following a "one-pot" incubation of 13C-substituted precursors with commercially available enzymes and cofactors of the glycolytic pathway. Since it has previously been shown that a wide variety of aldehydes serve as acceptable substrates for the final rabbit muscle aldolase-catalyzed condensation step, the method can potentially be applied to prepare a wide variety of 13C-substituted sugars and sugar phosphates.

Alanine↗