Testosterone and β-oestradiol prevent inward remodelling of rat small mesenteric arteries: role of NO and transglutaminase

2013 ◽  
Vol 124 (12) ◽  
pp. 719-728 ◽  
Author(s):  
Lara del Campo ◽  
Bilge Guvenc Tuna ◽  
Mercedes Ferrer ◽  
Ed van Bavel ◽  
Erik N.T.P. Bakker
Keyword(s):  
Sex Hormones ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Preventive Effect ◽  
Female Wistar Rats ◽  
Males And Females ◽  
Synthase Inhibitor ◽  
Dose Dependent

Increasing evidence shows that sex hormones exert a protective effect on the vasculature, especially in the regulation of the active vasomotor responses. However, whether sex hormones affect vascular remodelling is currently unclear. In the present study, we tested the hypothesis that testosterone in males and β-oestradiol in females prevent inward remodelling, possibly through inhibition of cross-linking activity induced by enzymes of the TG (transglutaminase) family. Small mesenteric arteries were isolated from male and female Wistar rats. Dose-dependent relaxation to testosterone and β-oestradiol was inhibited by the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester), confirming that these hormones induce NO release. When arteries were cannulated, pressurized and kept in organ culture with ET-1 (endothelin-1) for 3 days we observed strong vasoconstriction and inward remodelling. Remodelling was significantly inhibited by testosterone in males, and by β-oestradiol in females. This preventive effect of sex hormones was not observed in the presence of L-NAME. Inward remodelling was also reduced by the inhibitor of TG L682.777, both in males and females. In arteries from female rats, ET-1 increased TG activity, and this effect was prevented by β-oestradiol. L-NAME induced a significant increase in TG activity in the presence of sex hormones in arteries from both genders. We conclude that testosterone and β-oestradiol prevent constriction-induced inward remodelling. Inward remodelling, both in males and females, depends on NO and TG activity. In females, inhibition of inward remodelling could be mediated by NO-mediated inhibition of TG activity.

Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries

2002 ◽  
Vol 103 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Nuria MINOVES ◽  
Gloria BALFAGÓN ◽  
Mercedes FERRER
Keyword(s):  
Sex Hormones ◽  
Nerve Impulse ◽  
No Synthase ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Female Sex ◽  
Female Sex Hormones ◽  
No Synthase Inhibitor ◽  
Ovx Rats ◽  
Synthase Inhibitor

This study examines the effects of female sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as the modulation of this response by neuronal NO. For this purpose, segments of denuded superior mesenteric artery from ovariectomized (OvX) female Sprague–Dawley rats and from control rats (in oestrus phase) were used. EFS induced frequency-dependent contractions, which were greater in segments from OvX rats than in those from control rats. The NO synthase inhibitor NG-nitro-l-arginine methyl ester strengthened EFS-elicited contractions to a greater extent in arteries from OvX rats than in those from control rats. Similar results were observed with the preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial neurotoxin capsaicin did not modify EFS-induced contractions in segments from either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP) induced concentration-dependent relaxation, which was greater in segments from control rats than in those from OvX rats. 8-Bromo-cGMP induced similar concentration-dependent relaxation in noradrenaline-precontracted segments from both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD) inhibitor, reduced the relaxation induced by SNP in segments from both groups of rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP in segments from OvX rats, but did not modify it in segments from control rats. EFS induced NO−2 formation, which was greater in segments from OvX than in those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve impulse propagation, abolished release in both cases. These results suggest that EFS induces greater neuronal NO release in mesenteric segments from OvX rats than in those from control rats and, although NO metabolism is also higher, the contribution of net neuronal NO in the vasomotor response to EFS is greater in segments from OvX rats than in those from control rats.

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α1- and α2-adrenoceptor activation

1997 ◽  
Vol 82 (6) ◽  
pp. 1918-1925 ◽  
Author(s):  
A. O. A. Zschauer ◽  
M. W. Sielczak ◽  
D. A. S. Smith ◽  
A. Wanner
Keyword(s):  
Smooth Muscle ◽  
Response Curve ◽  
Bronchial Artery ◽  
No Synthase ◽  
Dependent Manner ◽  
Cyclooxygenase Inhibitor ◽  
Synthase Inhibitor ◽  
The Right ◽  
Dose Dependent

Zschauer, A. O. A., M. W. Sielczak, D. A. S. Smith, and A. Wanner. Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α1- and α2-adrenoceptor activation. J. Appl. Physiol. 82(6): 1918–1925, 1997.—The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150–300 μm in diameter) and the role of α1- and α2-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and N G-nitro-l-arginine methyl ester [l-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The α1-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (α1-AR agonist) induced a dose-dependent contraction that was potentiated byl-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the α2-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (α2-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of α1- and α2-ARs on both smooth muscle and endothelium. Activation of the α1- and α2-ARs on the smooth muscle causes contraction, whereas activation of the endothelial α1- and α2-ARs induces relaxation through release of NO (α1-ARs) and a prostanoid (α2-ARs).

The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca – salt treated rats

2018 ◽  
Vol 37 (3) ◽  
Author(s):  
Marzieh Kafami ◽  
Mahmoud Hosseini ◽  
Saeed Niazmand ◽  
Esmaeil Farrokhi ◽  
Mosa Al-Reza Hajzadeh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Sex Hormones ◽  
Active Oxygen Species ◽  
Oxygen Species ◽  
Research Needs ◽  
Ang Ii ◽  
Detailed Mechanism ◽  
Female Wistar Rats

Abstract Background Although numerous studies have proven that estrogen (Est) has a protective effect on the development of hypertension, more research needs to be done to show its detailed mechanism in a variety of hypertension. The important role of active oxygen species in blood pressure is well defined. We examined whether or not sex hormones change the growth of reactive oxygen species (ROS) ‎in kidneys after central microinjection of angiotensin II (Ang II).‎ Materials and methods Female Wistar rats, 8 weeks old (200 ± 10 g) were used in this study. The animal groups were (1) Sham, (2) Ovariectomy (OVX), (3) Sham-Hypertension (Sham-Hyper), (4) OVX-Hypertension (OVX-Hyper), (5) Sham-Hyper-Est, (6) OVX-Hyper-Est‎;‎ (7) Sham-Hyper-Testosterone (Tst) and (8) OVX-Hyper-Tst. Solutions of 1% NaCl and 0.1 KCl ‎were used and desoxycorticostrone (doca-salt) was injected (45 mg/kg) 3 times a week in Hypertension groups. Estradiol and Tst (2 mg/kg and ‎5 mg/kg‎; daily; subcutaneously) for 4 weeks. Ang II (50 μM, 5 μL) was microinjected by intracerebroventricular ( i.c.v.) infusion and malondialdehyde (MDA) and thiol in the kidneys were measured. Results MDA in the kidneys was increased by Ang II and doca-salt treatments. Both estradiol and Tst decreased the kidney’s MDA. The level of thiol was higher in Hyper ‎groups and reversed after treatment with estradiol and Tst. Conclusions Our findings suggest that central effect of Ang II on blood pressure and kidney ‎disease is accompanied with increased levels of oxidative stress in the kidneys. Indeed sex hormones change the ROS level in the kidneys after central ‎microinjection of Ang II.‎‎

Role of sex hormones in development of chronic mountain sickness in rats

1994 ◽  
Vol 77 (1) ◽  
pp. 427-433 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
J. C. Leiter ◽  
T. Brinck-Johnsen ◽  
R. P. Smith
Keyword(s):  
Gender Differences ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sex Hormones ◽  
Systolic Pressure ◽  
Female Rats ◽  
Hypoxic Exposure ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

Functional heterogeneity of endothelial P2 purinoceptors in the cerebrovascular tree of the rat

1999 ◽  
Vol 277 (3) ◽  
pp. H893-H900 ◽  
Author(s):  
Junping You ◽  
T. David Johnson ◽  
Sean P. Marrelli ◽  
Robert M. Bryan
Keyword(s):  
Cerebral Arteries ◽  
No Synthase ◽  
Third Order ◽  
Selective Agonist ◽  
Middle Cerebral Arteries ◽  
Spontaneous Tone ◽  
A Minor ◽  
Calcium Activated Potassium Channel ◽  
Dose Dependent

The effects of stimulating P2Y1 or P2Y2 purinoceptors on the endothelium of isolated middle cerebral arteries (MCAs), third-order branches of the MCA (bMCAs), and penetrating arterioles (PAs) of the rat were studied. After pressurization and development of spontaneous tone (25% contraction), resting diameters for MCAs, bMCAs, and PAs were 203 ± 5 ( n = 50), 99 ± 2 ( n = 42), and 87 ± 2 μm ( n = 53), respectively. Luminal application of the P2Y1-selective agonist 2-methylthioadenosine 5′-triphosphate elicited dose-dependent dilations (or loss of intrinsic tone) in MCAs but not in bMCAs or PAs. The dilation in MCAs was completely blocked by removal of the endothelium or by nitro-l-arginine methyl ester (10−5 M), an inhibitor of NO synthase. Luminal application of the P2Y2-selective agonist ATP elicited dilations in MCAs, bMCAs, and PAs. Removal of the endothelium abolished the dilations in all vessel groups. Dilations in MCAs have been shown to involve both NO and endothelium-derived hyperpolarizing factor (EDHF). The dilations in bMCAs and PAs had a minor NO component and prominent EDHF component; that is, 1) the dilations to ATP were not diminished by the combined inhibition of NO synthase and cyclooxygenase, 2) the dilations were accompanied by significant hyperpolarizations of the vascular smooth muscle (∼15 mV), and 3) the dilations were completely abolished by the calcium-activated potassium channel blocker charybdotoxin. We concluded that the role of NO in purinoceptor-induced dilations diminishes along the cerebrovascular tree in the rat, whereas the role of EDHF becomes more prominent.

Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle?

1995 ◽  
Vol 268 (2) ◽  
pp. G207-G214 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
V. Martinez ◽  
M. Jimenez ◽  
E. Gonalons ◽  
P. Vergara
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Motor Pattern ◽  
No Synthase ◽  
Phase Iii ◽  
Motor Patterns ◽  
No Donor ◽  
Postprandial State ◽  
Synthase Inhibitor

The main objective was to study the role of nitric oxide (NO) in the conversion of migrating myoelectric complexes (MMC) to the irregular electrical activity characteristic of the postprandial state. Both rats and chickens were implanted with electrodes for electromyography in the small intestine. Intravenous infusion of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, induced an organized MMC-like pattern in fed rats. Infusion of sodium nitroprusside, a NO donor, disrupted the MMC, inducing a postprandial-like motor pattern in fasting rats. Similarly, in chickens L-NNA mimicked the fasting pattern, consisting of a shortening of phase II, enlargement of phase III, orad displacement of the origin of the MMC, and an increase in the speed of phase III propagation. An inhibition of NO synthesis seems to be involved in the induction of the fasting motor pattern, whereas an increase of NO mediates the occurrence of the fed pattern. It is suggested that NO might be the final mediator in the control of small intestine motor patterns.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

scholarly journals Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones

2000 ◽  
Vol 279 (4) ◽  
pp. F664-F670 ◽  
Author(s):  
A. Marjan G. Verhagen ◽  
Diana M. A. Attia ◽  
Hein A. Koomans ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Sex Hormones ◽  
Oxide System ◽  
Female Rats ◽  
Male Rats ◽  
Time Control ◽  
Ovx Rats ◽  
Increased Sensitivity ◽  
Dose Dependent Increase

Men are at greater risk for renal injury than women. We studied whether male rats are more sensitive to the hypertensive and proteinuric effects of chronic nitric oxide sythase (NOS) inhibition than female rats. In addition, we studied whether androgens or estrogens are responsible for differences in sensitivity to proteinuria induced by chronic NOS inhibition. Females and males were treated with 10, 20, 30, and 100 mg/l N ω-nitro-l-arginine (l-NNA) during 24 wk. Systolic blood pressure (SBP) and proteinuria were measured regularly and compared with time-control measurements in control females and males. In females and males treatment with 10 mg/l l-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l l-NNA resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/ll-NNA were resistant to the development of proteinuria: maximum values were 16 ± 7 and 46 ± 21, respectively, vs. 16 ± 3 mg/day in controls, whereas males treated with those doses showed an increase in proteinuria [139 ± 35 ( P< 0.05) and 318 ± 82 ( P < 0.01), respectively, vs. 55 ± 11 mg/day in controls]. Treatment with 100 mg/ll-NNA increased proteinuria similarly in both females and males. To study the role of sex hormones in differences in sensitivity to proteinuria induced by mild chronic NOS inhibition, treatment with 20 mg/l l-NNA was repeated in ovariectomized (Ovx) and orchidectomized rats. Ovariectomy did not affect the increase in SBP caused by 20 mg/l l-NNA, but, in contrast to intact females, this dose of l-NNA did cause Ovx rats to develop proteinuria (51 ± 16 vs. 16 ± 7 mg/day in control Ovx rats; P < 0.05). Orchidectomy completely prevented the increased SBP as well as proteinuria induced by 20 mg/ll-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male rats to proteinuria induced by mild chronic NOS inhibition. Risk factors associated with a compromised nitric oxide system may be more detrimental to the kidney in men than in women.

Facilitatory role of NO in neural norepinephrine release in the rat kidney

2002 ◽  
Vol 282 (5) ◽  
pp. R1436-R1442 ◽  
Author(s):  
Hideki Tanioka ◽  
Koichi Nakamura ◽  
Shinsei Fujimura ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Renal Perfusion ◽  
No Synthase ◽  
Pressure Response ◽  
Renal Nerve ◽  
Nos Inhibitors ◽  
Synthase Inhibitor

We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and renal norepinephrine (NE) efflux. Nonselective NO synthase (NOS) inhibitors [ N ω-nitro-l-arginine methyl ester (l-NAME) or N ω-nitro-l-arginine], but not a selective neuronal NO synthase inhibitor (7-nitroindazole sodium salt), suppressed the NE efflux response and enhanced the perfusion pressure response. Pretreatment with l-arginine prevented the effects of l-NAME on the RNS-induced responses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), which eliminates NO by oxidizing it to NO2, suppressed the NE efflux response, whereas the perfusion pressure response was less susceptible to carboxy-PTIO. 8-Bromoguanosine cGMP suppressed and a guanylate cyclase inhibitor [4 H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS-induced perfusion pressure response, but neither of these drugs affected the NE efflux response. These results suggest that endogenous NO facilitates the NE release through cGMP-independent mechanisms, NO metabolites formed after NO2 rather than NO itself counteract the vasoconstriction, and neuronal NOS does not contribute to these modulatory mechanisms in the sympathetic nervous system of the rat kidney.

scholarly journals Sex Differences in Otolaryngology: Focus on the Emerging Role of Estrogens in Inflammatory and Pro-Resolving Responses

2021 ◽  
Vol 22 (16) ◽  
pp. 8768
Author(s):  
Sheng-Dean Luo ◽  
Tai-Jan Chiu ◽  
Wei-Chih Chen ◽  
Ching-Shuen Wang
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Immune Cells ◽  
Vocal Fold ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Proinflammatory Responses ◽  
Males And Females ◽  
Nose And Throat

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in ENT diseases are linked to the level of sex hormones. The sex hormone receptors are present on a wide variety of immune cells; therefore, it is evident that they play crucial roles in regulating the immune system and hence affect the disease progression of ENT diseases. In this review, we focus on how sex hormones, particularly estrogens, regulate ENT diseases, such as chronic rhinosinusitis, vocal fold polyps, thyroid cancer, Sjögren’s syndrome, and head and neck cancers, from the perspectives of inflammatory responses and specialized proresolving mediator-driven resolution. This paper aims to clarify why considering sex differences in the field of basic and medical research on otolaryngology is a key component to successful therapy for both males and females in the future.

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