Biphasic response to acetylcholine in human veins in vivo: the role of the endothelium

1990 ◽  
Vol 78 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Joe Collier ◽  
Patrick Vallance
Keyword(s):  
Dose Response ◽  
Distilled Water ◽  
Low Doses ◽  
Biphasic Response ◽  
Dorsal Hand ◽  
Before And After ◽  
Higher Doses ◽  
Made In

1. The dose-response to acetylcholine has been examined in dorsal hand veins of healthy volunteers before and after removal of the endothelium. 2. Measurements were made in single dorsal hand veins during local infusions of acetylcholine. The vein was irrigated with distilled water to remove the endothelium. Dilator studies were performed in vessels preconstricted by a continuous infusion of noradrenaline. 3. In the endothelium-intact vessel the dose-response to acetylcholine was biphasic; low doses produced venodilatation with higher doses causing venoconstriction. 4. Dilatation to low doses of acetylcholine was abolished by prior irrigation with distilled water, consistent with denudation of the endothelium by this process. Irrigation augmented the constriction seen in response to higher doses of acetylcholine. 5. This is the first demonstration of an endothelium-dependent biphasic dose-response to acetylcholine in man. The results raise questions as to the possible physiological actions of endogenous acetylcholine and as to the use of the acetylcholine dose-response curve as a marker of endothelial function.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

scholarly journals An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta)

2007 ◽  
Vol 292 (4) ◽  
pp. E1000-E1009 ◽  
Author(s):  
Bret M. Windsor-Engnell ◽  
Etsuko Kasuya ◽  
Masaharu Mizuno ◽  
Kim L. Keen ◽  
Ei Terasawa
Keyword(s):  
Precocious Puberty ◽  
Rhesus Monkeys ◽  
Gaba Release ◽  
Good Tool ◽  
Subsequent Increase ◽  
Female Rhesus ◽  
Before And After ◽  
Lhrh Release

We have previously shown that a decrease in γ-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 ± 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 ± 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600–1200 and 1800–2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 ± 0.2 mo) than in sham/controls (25.5 ± 0.9 mo, P < 0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18–20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

Role of endothelin receptor subtypes in the in vivo regulation of renal function

1995 ◽  
Vol 268 (3) ◽  
pp. F455-F460 ◽  
Author(s):  
A. L. Clavell ◽  
A. J. Stingo ◽  
K. B. Margulies ◽  
R. R. Brandt ◽  
J. C. Burnett
Keyword(s):  
Sodium Excretion ◽  
Urine Osmolality ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Low Doses ◽  
Renal Vasoconstriction ◽  
Etb Receptor ◽  
Diuretic Response

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.

Further observations of aldosterone response in barnacle muscle fibers

1983 ◽  
Vol 245 (3) ◽  
pp. E230-E238
Author(s):  
R. B. Tallitsch
Keyword(s):  
Dose Response ◽  
Muscle Fibers ◽  
External Application ◽  
Barnacle Muscle ◽  
Mitochondrial Inhibitors ◽  
Glucocorticoid Response ◽  
Saturation Kinetics ◽  
Barnacle Muscle Fibers

Work with single muscle fibers from the barnacle Balanus nubilus has revealed that these fibers can be rendered sensitive to external application of aldosterone by preexposing the barnacle in vivo to the steroid for 16 h. Experiments investigating the dose-response relationship, glucocorticoid sensitivity of the preparation, and the role of the mitochondria in the aldosterone response in this preparation are presented. It is demonstrated that saturation kinetics may be seen in the dose-response curve if care is taken to isolate only fibers from animals that are in midmolt cycle. Data is presented that demonstrated a specific mineralocorticoid response to aldosterone in this preparation rather than a combined mineralocorticoid-glucocorticoid response, as has been demonstrated in other preparations. Experiments investigating the role of the mitochondrial inhibitors and substrates suggest that aldosterone modulates Na efflux in barnacle muscle fibers by altering mitochondrial function, presumably at the level of succinic hydrogenase.

scholarly journals Targeting Wnt/β-Catenin Pathway for Developing Therapies for Hair Loss

2020 ◽  
Vol 21 (14) ◽  
pp. 4915 ◽  
Author(s):  
Bu Young Choi
Keyword(s):  
Hair Loss ◽  
Hair Growth ◽  
In Vivo Studies ◽  
Intracellular Targets ◽  
Remarkable Progress ◽  
Made In

Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis of hair loss and identifying valid intracellular targets for designing effective therapies for hair loss treatment. Whereas a variety of growth factors and signaling pathways have been implicated in hair cycling process, the activation of Wnt/β-catenin signaling plays a central role in hair follicle regeneration. Several plant-derived chemicals have been reported to promote hair growth by activating Wnt/β-catenin signaling in various in vitro and in vivo studies. This mini-review sheds light on the role of Wnt/β-catenin in promoting hair growth and the current progress in designing hair loss therapies by targeting this signaling pathway.

Nitric oxide accounts for histamine-induced increases in macromolecular extravasation

1994 ◽  
Vol 266 (6) ◽  
pp. H2369-H2373 ◽  
Author(s):  
W. G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Fluorescent Microscopy ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Subsequent Activation ◽  
Ly 83583

The goal of this study was to determine the role of nitric oxide in histamine-induced increases in macromolecular extravasation in the hamster cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt = 70,000 K) to examine extravasation from postcapillary venules in response to histamine before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in extravasation of macromolecules were quantitated counting the number of venular leaky sites. Histamine (1.0 and 5.0 microM) increased the number of venular leaky sites from zero (basal conditions) to 11 +/- 1 and 21 +/- 2/0.11 cm2, respectively. Superfusion of L-NMMA (1.0 microM) and LY-83583 (1.0 microM) significantly decreased histamine-induced formation of venular leaky sites, whereas L-arginine (100 microM) potentiated histamine-induced formation of venular leaky sites. In contrast, superfusion of NG-monomethyl-D-arginine (1.0 microM) did not inhibit the formation of venular leaky sites in response to histamine. Thus the findings of the present study suggest that production of nitric oxide, and subsequent activation of guanylate cyclase, plays an important role in macromolecular efflux in vivo in response to histamine.

In vivo perspective study about the effects of weekly low dose administration of zoledronic acid (ZA) on angiogenesis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3558-3558
Author(s):  
D. Santini ◽  
B. Vincenzi ◽  
F. Battistoni ◽  
S. Galluzzo ◽  
L. Rocci ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Low Doses ◽  
Dose Administration ◽  
Before And After ◽  
Endothelial Growth Factor ◽  
First Time

3558 Purpose: Recent data have demonstrated in preclinical tumor models an antiangiogenic and antitumor activity of low weekly doses of ZA. As a consequence, the purpose of this study was to confirm these data, evaluating in cancer patients the modifications in angiogenic cytokines levels following repeated weekly low doses of ZA. Experimental Design: 26 consecutive cancer patients with bone metastases treated, for the first time, with four weekly doses of 1 mg of ZA followed by standard doses (4 mg every 28 days) were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) at different time points: just before and after 1, 7, 14, 21, 28, 56 and 84 days following the first disphosphonate infusion. Results: Basal serum VEGF median levels were significantly decreased just after 7 days (-29.7%) (with only one weekly infusion) (P=0.038), This significant decrease of circulating VEGF levels persisted 14(-33.2%), 21 (-39.4%), 28(-31.8%), 56(-33.6%) and 84(-27.9%) days after the first infusion (respectively, P=0.002, P=0.001, P=0.008, P=0.002, P=0.014). Conclusions: This study confirms, for the first time in humans, that weekly low doses of zoledronic acid could have antiangiogenic properties through a significant and long lasting decrease of VEGF serum levels. No significant financial relationships to disclose.

Neutralization of Enoxaparine-lnduced Bleeding by Protamine Sulfate

1990 ◽  
Vol 63 (02) ◽  
pp. 271-274 ◽  
Author(s):  
J Van Ryn-McKenna ◽  
L Cai ◽  
F A Ofosu ◽  
J Hirsh ◽  
M R Buchanan
Keyword(s):  
Blood Loss ◽  
Unfractionated Heparin ◽  
Ex Vivo ◽  
Factor Xa ◽  
Protamine Sulfate ◽  
Low Molecular Weight Heparins ◽  
Before And After ◽  
Made In

SummaryIt has been suggested that protamine sulfate is a poor antidote for the bleeding side-effeets of low molecular weight heparins (LMWHs) in vivo, since protamine sulfate does not completely neutralize the anti-factor Xa activity of LMWHs in vitro or ex vivo. Therefore, we performed experiments to compare directly the abilities of protamine sulfate to neutralize the anticoagulant activities of the LMWH, enoxaparine, and unfractionated heparin ex vivo, with its ability to neutralize the bleeding side-effeets of both compounds in vivo. Bleeding was measured as the amount of blood lost from 5 cuts made in rabbits ears before and after treatment with enoxaparine or unfractionated heparin ± protamine sulfate. Plasma anti-factor Xa and anti-thrombin activities ex vivo, were measured chromogenically. Doses of 400 and 1,500 anti-factor Xa U/kg of heparin and enoxaparine, respectively, were required to enhance blood loss to the same extent. Protamine sulfate completely neutralized blood loss induced by both compounds, but did not neutralize the anti-factor Xa nor antithrombin activities ex vivo. We conclude that protamine sulfate is an effective antidote for the bleeding side-effeets of enoxaparine and unfractionated heparin, despite its inability to completely neutralize their anticoagulant activities.

Role of LPXRFamide peptide in the neuroendocrine regulation of reproduction in fish

2011 ◽  
Vol 6 (5) ◽  
pp. 853-860 ◽  
Author(s):  
Md. Shahjahan ◽  
Hironori Ando
Keyword(s):  
Gonadal Development ◽  
Gonadotropin Releasing Hormone ◽  
Fish Reproduction ◽  
Lower Vertebrates ◽  
Hypothalamic Control ◽  
G Protein Coupled ◽  
Made In

AbstractThe decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin (GTH) secretion. This review focuses on a family of neuropeptides, LPXRFamide (LPXRFa) peptides, which have been implicated in the regulation of GTH secretion. LPXRFa acts on the pituitary via a G protein-coupled receptor, LPXRFa-R, to enhance gonadal development and maintenance by increasing gonadotropin release and synthesis. Because LPXRFa exists and functions in several fish species, LPXRFa is considered to be a key neurohormone in fish reproduction control. The precursors to LPXRFamide peptides encoded plural LPXRFamide peptides and were highly divergent in vertebrates, particularly in lower vertebrates. Tissue distribution analyses indicated that LPXRFamide peptides were highly concentrated in the hypothalamus and other brainstem regions. In view of the localization and expression of LPXRFamide peptides in the hypothalamo-hypophysial system, LPXRFamide peptide in fish increase GTH release in vitro and in vivo. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of LPXRFa, a newly discovered key neurohormone.

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