scholarly journals Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms

2000 ◽  
Vol 279 (2) ◽  
pp. H610-H618 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Cerebral Arteries ◽  
Gonadal Hormones ◽  
No Synthase ◽  
Male Rats ◽  
Male Rat ◽  
Myogenic Tone ◽  
Channel Blockers ◽  
Luminal Diameter ◽  
Nos Inhibitor

Gender is known to influence the incidence and severity of cerebrovascular disease. In the present study, luminal diameter was measured in vitro in pressurized middle cerebral artery segments from male rats that were either untreated, orchiectomized (ORX), ORX with testosterone treatment (ORX+TEST), or ORX with estrogen treatment (ORX+EST). The maximal passive diameters (0 Ca2+ + 3 mM EDTA) of arteries from all four groups were similar. In endothelium-intact arteries, myogenic tone was significantly greater in arteries from untreated and ORX+TEST compared with arteries from either ORX or ORX+EST. During exposure to N G-nitro-l-arginine-methyl ester (l-NAME), an NO synthase (NOS) inhibitor, myogenic tone significantly increased in all groups. The effect of l-NAME was significantly greater in arteries from untreated and ORX+EST compared with arteries from ORX and ORX+TEST rats. Differences in myogenic tone between ORX and ORX+TEST persisted after inhibition of NOS. After endothelium removal or inhibition of the cyclooxygenase pathway combined with K+ channel blockers, myogenic tone differences between ORX and ORX+TEST were abolished. Wall thickness and forced dilation were not significantly different between arteries from ORX and ORX+TEST. Our data show that gonadal hormones affect myogenic tone in male rat cerebral arteries through NOS- and/or endothelium-dependent mechanisms.

Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries

1998 ◽  
Vol 275 (1) ◽  
pp. H292-H300 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
No Production ◽  
Luminal Diameter ◽  
Underlying Mechanisms ◽  
Synthase Inhibitor ◽  
Endothelial Nitric Oxide ◽  
Dependent Mechanism

Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (Ovx), or ovariectomized with estrogen replacement (Ovx + Est). The maximal passive diameters (0 Ca2++ 1 mM EDTA) of arteries from all four groups were identical. In response to a series of 10-mmHg step increases in transmural pressure (20–80 mmHg), myogenic tone was greater and vascular distensibility less in arteries from males and Ovx females compared with arteries from either untreated or Ovx + Est females. In the presence of N G-nitro-l-arginine methyl ester (l-NAME; 1 μM), an NO synthase inhibitor, myogenic tone was increased in all arteries, but the differences among arteries from the various groups were abolished. Addition ofl-arginine (1 mM) in the presence of l-NAME restored the differences in myogenic tone, suggesting that estrogen works through an NO-dependent mechanism in cerebral arteries. To determine the target of NO-dependent modulation of myogenic tone, we used tetraethylammonium (TEA; 1 mM) to inhibit large-conductance, calcium-activated K+(BKCa) channels. In the presence of TEA, the myogenic tone of arteries from all groups increased significantly; however, myogenic tone in arteries from males and Ovx females remained significantly greater than in arteries from either untreated or Ovx + Est females. This suggests that activity of BKCa channels influences myogenic tone but does not directly mediate the effects of estrogen. Estrogen appears to alter myogenic tone by increasing cerebrovascular NO production and/or action.

Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver

1984 ◽  
Vol 247 (3) ◽  
pp. G226-G230
Author(s):  
R. B. Kirkpatrick ◽  
B. G. Kraft
Keyword(s):  
Bile Acid ◽  
Specific Activity ◽  
Male Rats ◽  
Male Rat ◽  
Estrogen Metabolism ◽  
Normal Male ◽  
Activity Levels ◽  
Receptor Kinetics ◽  
Streptozotocin Induced Diabetes

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.

The Effects of Melatonin and Serotonin on Blood Flow Fraction and Testosterone Metabolism in Selected Organs of the Male Rat

1973 ◽  
Vol 51 (5) ◽  
pp. 313-318 ◽  
Author(s):  
G. A. Kinson ◽  
Nora E. MacDonald ◽  
C-C. Liu
Keyword(s):  
Blood Flow ◽  
Nicotinamide Adenine Dinucleotide ◽  
Male Rats ◽  
Male Rat ◽  
Blood Levels ◽  
Testosterone Metabolism ◽  
Melatonin Administration ◽  
Distribution Of Cardiac Output ◽  
Fractional Distribution

The fractional distribution of cardiac output to the testes, adrenals, liver, and kidneys and the conversion of testosterone to 4-androstenedione by hepatic and renal homogenates in vitro were measured 4 weeks after implantation of male rats with melatonin and serotonin. The fractional blood flow to these organs was not significantly influenced by the indoles. There was, however, a tendency for the adrenal fraction to be lower in indole-treated rats. Blood levels of corticosterone in these animals were reduced, but significantly so only in the rats implanted with serotonin. The ability of liver preparations to metabolize testosterone in the presence of excess nicotinamide–adenine dinucleotide was enhanced after treatment with both indoles suggesting that at least one of the 17β-hydroxysteroid dehydrogenases had been stimulated. In the case of the kidney, melatonin administration gave rise to depression of the NAD-linked conversion whereas serotonin treatment caused reductions in testosterone conversions in the presence of either NAD or NADP.

scholarly journals In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Body Weight Gain ◽  
Biologically Active ◽  
Male Rats ◽  
Male Rat ◽  
Gh Secretion ◽  
Adult Rat ◽  
Testosterone Secretion

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.

Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior

2002 ◽  
Vol 283 (6) ◽  
pp. H2260-H2267 ◽  
Author(s):  
George Osol ◽  
Johan Fredrik Brekke ◽  
Keara McElroy-Yaggy ◽  
Natalia I. Gokina
Keyword(s):  
Cerebral Arteries ◽  
Peripheral Resistance ◽  
Force Production ◽  
Cytosolic Calcium ◽  
Myogenic Tone ◽  
Wall Tension ◽  
Resistance Arteries ◽  
Cellular Mechanisms ◽  
Initial Development

Myogenic behavior, prevalent in resistance arteries and arterioles, involves arterial constriction in response to intravascular pressure. This process is often studied in vitro by using cannulated, pressurized arterial segments from different regional circulations. We propose a comprehensive model for myogenicity that consists of three interrelated but dissociable phases: 1) the initial development of myogenic tone (MT), 2) myogenic reactivity to subsequent changes in pressure (MR), and 3) forced dilatation at high transmural pressures (FD). The three phases span the physiological range of transmural pressures (e.g., MT, 40–60 mmHg; MR, 60–140 mmHg; FD, >140 mmHg in cerebral arteries) and are characterized by distinct changes in cytosolic calcium ([Ca2+]i), which do not parallel arterial diameter or wall tension, and therefore suggest the existence of additional regulatory mechanisms. Specifically, the development of MT is accompanied by a substantial (200%) elevation in [Ca2+]i and a reduction in lumen diameter and wall tension, whereas MR is associated with relatively small [Ca2+]i increments (<20% over the entire pressure range) despite considerable increases in wall tension and force production but little or no change in diameter. FD is characterized by a significant additional elevation in [Ca2+]i (>50%), complete loss of force production, and a rapid increase in wall tension. The utility of this model is that it provides a framework for comparing myogenic behavior of vessels of different size and anatomic origin and for investigating the underlying cellular mechanisms that govern vascular smooth muscle mechanotransduction and contribute to the regulation of peripheral resistance.

scholarly journals Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

2004 ◽  
Vol 181 (2) ◽  
pp. 223-231 ◽  
Author(s):  
V Viau ◽  
MJ Meaney
Keyword(s):  
Feedback Regulation ◽  
High Plasma ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosteroid Binding Globulin ◽  
Low Testosterone

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml), plasma adrenocorticotropin and beta-endorphin/beta-lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( approximately 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( approximately 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro

1990 ◽  
Vol 122 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Elio Messi ◽  
Mariarosa Zanisi ◽  
Luciano Martini
Keyword(s):  
Feedback Control ◽  
Experimental Period ◽  
Feedback Mechanism ◽  
Male Rats ◽  
Male Rat ◽  
Gnrh Analogue ◽  
Feedback Systems ◽  
Gnrh Secretion ◽  
Gnrh Release

Abstract. Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6, Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered.

scholarly journals Effects of Chronic Ethanol on Hepatic and Renal CYP2C11 in the Male Rat: Interactions with the Janus-Kinase 2-Signal Transducer and Activators of Transcription Proteins 5b Pathway

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3969-3976 ◽  
Author(s):  
T. M. Badger ◽  
M. J. J. Ronis ◽  
S. J. Frank ◽  
Y. Chen ◽  
L. He
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Serum Testosterone ◽  
Janus Kinase ◽  
Chronic Ethanol ◽  
Male Rats ◽  
Male Rat ◽  
Signal Transducer ◽  
Transduction Pathway

Abstract Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8–10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect.

Quantification of the Uncertainties in Extrapolating From In Vitro Androgen Receptor Antagonism to In Vivo Hershberger Assay Endpoints and Adverse Reproductive Development in Male Rats

2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Adverse Outcome ◽  
In Utero ◽  
Male Rats ◽  
Male Rat ◽  
Rat Offspring ◽  
Hershberger Assay ◽  
Key Events

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of &lt; 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage

2002 ◽  
Vol 283 (6) ◽  
pp. H2217-H2225 ◽  
Author(s):  
Masanori Ishiguro ◽  
Corey B. Puryear ◽  
Erica Bisson ◽  
Christine M. Saundry ◽  
David J. Nathan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Rabbit Model ◽  
Small Diameter ◽  
Myogenic Tone ◽  
The Impact ◽  
Intravascular Pressure

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100–200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (∼twofold) to pressure within the physiological range of 60–100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.

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