Norepinephrine sensitivity of mesenteric veins in pregnant rats

1990 ◽  
Vol 259 (4) ◽  
pp. R753-R759 ◽  
Author(s):  
M. Hohmann ◽  
T. M. Keve ◽  
G. Osol ◽  
M. K. McLaughlin
Keyword(s):  
Nerve Stimulation ◽  
Sympathetic Nerves ◽  
Transmural Pressure ◽  
Neuronal Uptake ◽  
Sprague Dawley ◽  
Adrenergic Stimulation ◽  
Pregnant Rats ◽  
Mesenteric Veins ◽  
Induced Changes

This study was designed to test the hypothesis that during the course of pregnancy there is a decrease in the venous response to adrenergic stimulation that is characterized by a decrease in venoconstriction to both exogenous norepinephrine (NE) and to transmural electric stimulation of endogenous sympathetic nerves. Capacitance-size mesenteric veins were removed from nonpregnant and early- (7/8 day) and late-pregnant (18/19 and 20/21 day) Sprague-Dawley rats and studied in vitro under pressurized conditions. Lumen diameter was measured continuously by a video-electronic method. There was a marked increase in the sensitivity of the veins to exogenous NE stimulation at the end of pregnancy, which was most dramatic at a transmural pressure of 6 compared with 2 mmHg. The increase in exogenous NE sensitivity was associated with a progressive decline in the response to transmural nerve stimulation during pregnancy. Cocaine, an inhibitor of neuronal uptake, resulted in a greater potentiation of the response to transmural nerve stimulation in the pregnant rats compared to controls, suggesting an increased reuptake mechanism during pregnancy. Additional studies in the pseudopregnant, lactating, and nonlactating rat suggested that the conceptus was necessary for the alterations in neural response but not for the increase in exogenous NE sensitivity. In conclusion there is a dramatic change in venous function during pregnancy in the rat that is characterized by a difference between endogenous and exogenous NE sensitivity. The fact that transmural pressure can profoundly affect exogenous NE sensitivity suggests that pregnancy-induced changes in venous volume could contribute to changes in venous reactivity.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Testosterone Decreases Placental Mitochondrial Content and Cellular Bioenergetics

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 176 ◽  
Author(s):  
Jay S. Mishra ◽  
Chellakkan S. Blesson ◽  
Sathish Kumar
Keyword(s):  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Structural Damage ◽  
Plasma Testosterone ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Testosterone Levels ◽  
Mitochondrial Copy Number ◽  
Maternal Testosterone

Placental mitochondrial dysfunction plays a central role in the pathogenesis of preeclampsia. Since preeclampsia is a hyperandrogenic state, we hypothesized that elevated maternal testosterone levels induce damage to placental mitochondria and decrease bioenergetic profiles. To test this hypothesis, pregnant Sprague–Dawley rats were injected with vehicle or testosterone propionate (0.5 mg/kg/day) from gestation day (GD) 15 to 19. On GD20, the placentas were isolated to assess mitochondrial structure, copy number, ATP/ADP ratio, and biogenesis (Pgc-1α and Nrf1). In addition, in vitro cultures of human trophoblasts (HTR-8/SVneo) were treated with dihydrotestosterone (0.3, 1.0, and 3.0 nM), and bioenergetic profiles using seahorse analyzer were assessed. Testosterone exposure in pregnant rats led to a 2-fold increase in plasma testosterone levels with an associated decrease in placental and fetal weights compared with controls. Elevated maternal testosterone levels induced structural damage to the placental mitochondria and decreased mitochondrial copy number. The ATP/ADP ratio was reduced with a parallel decrease in the mRNA and protein expression of Pgc-1α and Nrf1 in the placenta of testosterone-treated rats compared with controls. In cultured trophoblasts, dihydrotestosterone decreased the mitochondrial copy number and reduced PGC-1α, NRF1 mRNA, and protein levels without altering the expression of mitochondrial fission/fusion genes. Dihydrotestosterone exposure induced significant mitochondrial energy deficits with a dose-dependent decrease in basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. In summary, our study suggests that the placental mitochondrial dysfunction induced by elevated maternal testosterone might be a potential mechanism linking preeclampsia to feto-placental growth restriction.

Response to cardiac sympathetic activation in transgenic mice overexpressing beta 2-adrenergic receptor

1996 ◽  
Vol 271 (2) ◽  
pp. H630-H636 ◽  
Author(s):  
X. J. Du ◽  
E. Vincan ◽  
D. M. Woodcock ◽  
C. A. Milano ◽  
A. M. Dart ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Nerve Stimulation ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Adrenergic Stimulation ◽  
Adrenergic Activity ◽  
Beta 2 ◽  
Stimulation Of

Transgenic mice have been created with 200-fold overexpression of beta 2-adrenergic receptors specifically in the heart. Cardiac function was studied in these transgenic mice and their controls at baseline and during isoproterenol perfusion or sympathetic nerve stimulation. The model used was an in situ buffer-perfused, innervated heart, and the left ventricle maximal derivative of pressure over time (dP/dtmax) and heart rate (HR) were measured. Basal HR and dP/dtmax were 30-40% higher in hearts from transgenic mice than controls. Electrical stimulation of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax in control hearts. Hearts from transgenic mice did not respond to isoproterenol. However, hearts from transgenic mice retained the HR response to nerve stimulation, and a small increase in dP/dtmax was also detected. Atenolol inhibited the response to nerve stimulation in control hearts but not that in hearts from transgenic mice. ICI-118551 inhibited the response in transgenic hearts. Basal HR and dP/dtmax were decreased by ICI-118551 only in transgenic hearts. Thus overexpression of cardiac beta 2-receptors modifies beta-adrenergic activity, but the responses to endogenous and exogenous adrenergic stimulation are affected differently.

scholarly journals β2-Adrenergic Receptor Signaling in Osteoblasts Contributes to the Catabolic Effect of Glucocorticoids on Bone

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1412-1422 ◽  
Author(s):  
Yun Ma ◽  
Jeffry S. Nyman ◽  
Huan Tao ◽  
Heather H. Moss ◽  
Xiangli Yang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Cells ◽  
Sympathetic Nerves ◽  
Bone Diseases ◽  
Autonomic Nerves ◽  
High Dose ◽  
Bone Homeostasis ◽  
Adrenergic Stimulation

Abstract The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the β2-adrenergic receptors (β2AR), and pharmacological or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that conditions that affect β2AR signaling in osteoblasts and/or sympathetic drive to bone may contribute to bone diseases. In this study, we show that dexamethasone stimulates the expression of the β2AR in differentiated primary calvarial osteoblasts, as measured by an increase in Adrβ2 mRNA and β2AR protein level after short-term dexamethasone treatment. Isoproterenol-induced cAMP accumulation and the expression of the β2AR target gene Rankl were also significantly increased after dexamethasone pretreatment, indicating that dexamethasone promotes the responsiveness of differentiated osteoblasts to adrenergic stimulation. These in vitro results led to the hypothesis that glucocorticoid-induced bone loss, provoked by increased endogenous or high-dose exogenous glucocorticoids given for the treatment of inflammatory diseases, might, at least in part, be mediated by increased sensitivity of bone-forming cells to the tonic inhibitory effect of sympathetic nerves on bone formation or their stimulatory effect on bone resorption. Supporting this hypothesis, both pharmacological and genetic β2AR blockade in mice significantly reduced the bone catabolic effect of high-dose prednisolone in vivo. This study emphasizes the importance of sympathetic nerves in the regulation of bone homeostasis and indicates that this neuroskeletal signaling axis can be modulated by hormones or drugs and contribute to enhance pathological bone loss.

scholarly journals Dra/AfaE Adhesin of Uropathogenic Dr/Afa+Escherichia coli Mediates Mortality in Pregnant Rats

2005 ◽  
Vol 73 (11) ◽  
pp. 7597-7601 ◽  
Author(s):  
K. Wroblewska-Seniuk ◽  
R. Selvarangan ◽  
A. Hart ◽  
R. Pladzyk ◽  
P. Goluszko ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Maternal Mortality ◽  
Double Mutant ◽  
Lethal Effect ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
E Coli

ABSTRACT Escherichia coli bearing adhesins of the Dr/Afa family frequently causes urogenital infections during pregnancy in humans and has been associated with mortality in pregnant rats. Two components of the adhesin, Dra/AfaE and Dra/AfaD, considered virulence factors, are responsible for bacterial binding and internalization. We hypothesize that gestational mortality caused by Dr/Afa+ E. coli is mediated by one of these two proteins, Dra/AfaE or Dra/AfaD. In this study, using afaE and/or afaD mutants, we investigated the role of the afaE and afaD genes in the mortality of pregnant rats from intrauterine infection. Sprague-Dawley rats, on the 17th day of pregnancy, were infected with the E. coli afaE + afaD and afaE afaD + mutants. The clinical E. coli strain (afaE + afaD +) and the afaE afaD double mutant were used as positive and negative controls, respectively. The mortality rate was evaluated 24 h after infection. The highest maternal mortality was observed in the group infected with the afaE + afaD + strain, followed by the group infected with the afaE + afaD strain. The mortality was dose dependent. The afaE afaD double mutant did not cause maternal mortality, even with the highest infection dose. The in vivo studies corresponded with the invasion assay, where the afaE + strains were the most invasive (afaE + afaD strain > afaE + afaD + strain), while the afaE mutant strains (afaE afaD + and afaE afaD strains) seemed to be noninvasive. This study shows for the first time that the afaE gene coding for the AfaE subunit of Dr/Afa adhesin is involved in the lethal outcome of gestational infection in rats. This lethal effect associated with AfaE correlates with the invasiveness of afaE + E. coli strains in vitro.

Neuronal and Vascular Reactivity in Isolated Perfused Kidneys during the Development of Spontaneous Hypertension

1978 ◽  
Vol 55 (s4) ◽  
pp. 233s-235s ◽  
Author(s):  
Michael G. Collis ◽  
Paul M. Vanhoutte
Keyword(s):  
Angiotensin Ii ◽  
Nerve Stimulation ◽  
Vascular Reactivity ◽  
Barium Chloride ◽  
Sympathetic Nerves ◽  
Spontaneous Hypertension ◽  
Neuronal Uptake ◽  
Young Control ◽  
Spontaneously Hypertensive ◽  
Renal Sympathetic

1. Vascular reactivity was studied in Tyrode solution perfused kidneys from young (7 weeks) and mature (4–6 months) spontaneously hypertensive rats (SH rats). 2. The response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats, both in control solution and after inhibition of the disposition of noradrenaline; both groups exhibited the same sensitivity to noradrenaline, angiotensin II and barium chloride. 3. The response to nerve stimulation was normal in kidneys from mature SH rats, but responses to noradrenaline, angiotensin II and barium chloride were greater than the control. 4. Cocaine potentiated the response to nerve stimulation more in the kidneys from mature SH rats than in those from the control rats. 5. The results suggest that renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension. 6. In the established phase of spontaneous hypertension the vascular reactivity to exogenous agonists is increased, probably as a consequence of high blood pressure; the more efficient neuronal uptake causes normalization of the response to sympathetic nerve stimulation.

scholarly journals Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity

2008 ◽  
Vol 104 (5) ◽  
pp. 1273-1280 ◽  
Author(s):  
Bradley J. Behnke ◽  
David C. Zawieja ◽  
Anatoliy A. Gashev ◽  
Chester A. Ray ◽  
Michael D. Delp
Keyword(s):  
Simulated Microgravity ◽  
Plasma Concentrations ◽  
Bed Rest ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Adrenergic Stimulation ◽  
Large Pressure ◽  
Arteries And Veins

Diminished constriction of arteries and veins following exposure to microgravity or bed rest is associated with a reduced ability to augment peripheral vascular resistance (PVR) and stroke volume during orthostasis. We tested the hypothesis that small mesenteric arteries and veins, which are not exposed to large pressure shifts during simulated microgravity via head-down tail suspension (HDT), will exhibit decrements in adrenergic constriction after HDT in rats. Small mesenteric arteries and veins from control (Con; n = 41) and HDT ( n = 35) male Sprague-Dawley rats were studied in vitro. Vasoactive responsiveness to norepinephrine (NE) in arteries (10−9 to 10−4 M) and veins (pressure-diameter responses from 2 to 12 cmH2O after incubation in 10−6 or 10−4 M NE) were evaluated. Plasma concentrations of atrial (ANP) and NH2-terminal prohormone brain (NT-proBNP) natriuretic peptides were also measured. In mesenteric arteries, sensitivity and maximal responsiveness to NE were reduced with HDT. In mesenteric veins there was a diminished venoconstriction to NE at any given pressure in HDT. Plasma concentrations of both ANP and NT-proBNP were increased with HDT, and maximal arterial and venous constrictor responses to NE after incubation with 10−7 M ANP or brain natriuretic peptide (BNP) were diminished. These data demonstrate that, in a vascular bed not subjected to large hydrodynamic differences with HDT, both small arteries and veins have a reduced responsiveness to adrenergic stimulation. Elevated levels of circulating ANP or NT-proBNP could adversely affect the ability of these vascular beds to constrict in vivo and conceivably could alter the intrinsic constrictor properties of these vessels with long-term exposure.

Estrogen replacement attenuates resistance artery adrenergic sensitivity via endothelial vasodilators

1997 ◽  
Vol 272 (5) ◽  
pp. H2264-H2270 ◽  
Author(s):  
M. C. Meyer ◽  
K. Cummings ◽  
G. Osol
Keyword(s):  
Blood Pressure ◽  
Peripheral Resistance ◽  
Mesenteric Arteries ◽  
Muscarinic Agonist ◽  
Estrogen Replacement ◽  
Resistance Artery ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Adrenergic Stimulation

The objective of this study was to determine whether chronic estrogen replacement alters adrenergic constriction and endothelium-dependent dilation in resistance arteries from the rat. Resistance-sized (< 200 microns) mesenteric arteries from castrated female Sprague-Dawley rats with (E2; 21 day, 0.5-mg pellet) and without (OvX) estrogen replacement were removed for in vitro study on a pressurized arteriograph system. Sensitivity to alpha-adrenergic constriction and the role of the endothelium in its modulation and of agonist-provoked endothelium-dependent relaxation were determined. Estrogen-treated rats had decreased heart rate as well as systolic and diastolic blood pressure. Arteries from estrogen-replaced rats were fivefold less sensitive to alpha 1-adrenergic stimulation with phenylephrine (50% effective concentration: E2, 3.2 +/- 1.1 microM; OvX, 0.6 +/- 0.2 microM; P < 0.05). This difference was abolished by endothelial denudation, blockade of cyclooxygenase (1 microM ibuprofen), or nitric oxide synthase blockade (0.24 mM N omega-nitro-L-arginine). There was no difference in muscarinic agonist-provoked relaxation or vascular smooth muscle sensitivity to prostacyclin or sodium nitroprusside. These results indicate that estrogen replacement decreases resistance artery adrenergic sensitivity by increasing the basal release of relaxing factors from the endothelium. This effect on small artery function may produce dual cardioprotective effects by decreasing peripheral resistance, blood pressure, and the likelihood of thrombosis.

Decreased in vitro responses to vasoconstrictors during gestation in normotensive and spontaneously hypertensive rats

1987 ◽  
Vol 65 (12) ◽  
pp. 2466-2471 ◽  
Author(s):  
G. Massicotte ◽  
J. St-Louis ◽  
A. Parent ◽  
E. L. Schiffrin
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Female Rats ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Pregnant Rats ◽  
Spontaneously Hypertensive ◽  
Vasoconstrictor Agents ◽  
Wistar Kyoto

We have investigated the in vitro vascular responses to vasoconstrictor agents in pregnant normotensive (Sprague–Dawley (SDR) and Wistar–Kyoto (WKR)) and spontaneously hypertensive rats (SHR) to measure the sensitivity and contractility of blood vessels of pregnant rats. In the perfused mesenteric vascular bed from rats on the 21st day of gestation, the concentration–response curves for the increase in perfusion pressure by arginine8-vasopressin and norepinephrine were displaced to the right by comparison to nonpregnant female rats when all strains of rats were considered together. The increase in EC50 to both agents in pregnant rats was from 1.3- to 2.7-fold in the mesenteric bed; SDR showed the highest increase in EC50, followed by SHR and WKR. No consistent effect was observed on the maximum response. Similar results were obtained in isolated portal veins for angiotensin II and norepinephrine, except that the increase in EC50 in pregnant rats was smaller in magnitude (from 1.0 to 1.7) and followed the same interstrain pattern. These data show that the decreased responsiveness to vasoconstrictor agents in pregnant rats observed in vitro is similar in normotensive and hypertensive rats and suggest that the factor(s) responsible for this effect is a phenomenon affecting vascular smooth muscle in both arteries and veins.

scholarly journals Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Nannan Chai ◽  
Hao Zhang ◽  
Lingxu Li ◽  
Xue Yu ◽  
Yan Liu ◽  
...  
Keyword(s):  
Cardiac Injury ◽  
Heart Weight ◽  
Cardiomyocyte Proliferation ◽  
Pregnant Rats ◽  
Mitochondrial Ros ◽  
Intrauterine Hypoxia ◽  
Heart Injury ◽  
Potential Strategy ◽  
Induced Changes

Intrauterine hypoxia (IUH) is a common intrauterine dysplasia that can cause programming of the offspring cardiovascular system. In this study, we hypothesized that placental treatment with spermidine (SPD) can prevent heart injury in neonatal offspring exposed to IUH. Pregnant rats were exposed to 21% O2 or 10% O2 (hypoxia) for 7 days prior to term or were exposed to hypoxia and intraperitoneally administered SPD or SPD+difluromethylornithine (DFMO) on gestational days 15-21. Seven-day-old offspring were then sacrificed to assess several parameters. Our results demonstrated that IUH led to decreased myocardial ornithine decarboxylase (ODC) and increased spermidine/spermine N1-acetyltransferase (SSAT) expression in the offspring. IUH also resulted in decreased offspring body weight, heart weight, cardiomyocyte proliferation, and antioxidant capacity and increased cardiomyocyte apoptosis and fibrosis. Furthermore, IUH caused mitochondrial structure abnormality, dysfunction, and decreased biogenesis and led to a fission/fusion imbalance in offspring hearts. In vitro, hypoxia induced mitochondrial ROS accumulation, decreased membrane potential, and increased fragmentation. Notably, all hypoxia-induced changes analyzed in this study were prevented by SPD. Thus, in utero SPD treatment is a potential strategy for preventing IUH-induced neonatal cardiac injury.

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