Mesenteric vascular responses to vasopressin during development of DOCA-salt hypertension in male and female rats

1995 ◽  
Vol 268 (1) ◽  
pp. R40-R49 ◽  
Author(s):  
J. N. Stallone

Deoxycorticosterone acetate (DOCA)-salt hypertension develops to a greater extent in male (M) than in female (F) rats. To determine the role of the vasculature, reactivity to arginine vasopressin (AVP) and prostanoid output were examined in the isolated perfused mesenteric vasculature of hypertensive (HT) and normotensive-control (NTC) M and F rats after acute (1-wk) and chronic (4-wk) DOCA-salt treatment. Systolic blood pressure was significantly higher in M than in F HT rats (187 +/- 3 vs. 151 +/- 3 mmHg after 4 wk; P < 0.02). After acute treatment, vascular reactivity to AVP (maximal perfusion pressure) in HT was elevated in M (181 +/- 18 mmHg; P < 0.02) but not in F (135 +/- 6 mmHg) compared with NTC (90 +/- 6 mmHg, M vs. 119 +/- 5 mmHg, F). After chronic treatment, vascular reactivity to AVP in HT was elevated in both sexes (P < 0.02), although more in F (175 +/- 13 mmHg) than in M (141 +/- 11 mmHg). In contrast, vascular responsiveness to phenylephrine did not differ significantly between M and F NTC or HT preparations after either acute or chronic treatment. Sex differences in basal and AVP-induced 6-ketoprostaglandin (6-keto-PG) F1 alpha and PGE2 output by HT and NTC vasculature were reciprocal to sex differences in the vasoconstriction responses to AVP. After acute treatment, AVP-stimulated 6-keto-PGF1 alpha output by HT was elevated slightly in F (33.6 +/- 1.7 ng/3 min; P < or = 0.02) but not in M (49.9 +/- 4.3 ng/3 min) compared with NTC (23.5 +/- 2.6 ng/3 min, F vs. 34.7 +/- 4.9 ng/3 min, M). After chronic treatment, output by HT was enhanced in both sexes (P < or = to 0.02), although more in M (109 +/- 15.4 ng/3 min) than in F (68 +/- 6.6 ng/3 min)> These findings suggest that sex differences in the relative balance between AVP-induced vasoconstriction and vasodilatory prostanoid release may contribute to male-female differences in mesenteric vascular reactivity to AVP in NT and that disturbances in this balance may be responsible, at least in part, for the sex- and time-dependent changes in reactivity to AVP observed during the development of DOCA-salt hypertension.

Author(s):  
Linnea R Freeman ◽  
Brandon S Bentzley ◽  
Morgan H James ◽  
Gary Aston-Jones

Abstract Background The prevalence of eating disorders, including binge eating disorder, is significantly higher in women. These findings are mirrored by preclinical studies, which indicate that female rats have a higher preference for palatable food and show greater binge-like eating compared with male rats. Methods Here, we describe a novel within-session behavioral-economic paradigm that allows for the simultaneous measurement of the intake at null cost (Q0) and normalized demand elasticity (α) of 3 types of palatable food (low fat, high fat, and chocolate sucrose pellets) via demand curve analysis. In light of evidence that the orexin (hypocretin) system is critically involved in reward and feeding behaviors, we also examined the role of orexin function in sex differences of economic demand for palatable foods. Results The novel within-session behavioral-economic approach revealed that female rats have higher intake (demand) than males for all palatable foods at low cost (normalized to body weight) but no difference in intake at higher prices, indicating sex-dependent differences in the hedonic, but not motivational, aspects of palatable food. Immediately following behavioral-economic testing, we observed more orexin-expressing neurons and Fos expression (measure of recent neural activation) in these neurons in female rats compared with male rats. Moreover, the orexin-1 receptor antagonist SB334867 reduced both low- and high-cost intake for palatable food in both male and female rats. Conclusions These findings provide evidence of higher demand at low prices for palatable food in females and indicate that these behavioral differences may be associated with sexual dimorphism in orexin system function.


2011 ◽  
Vol 301 (5) ◽  
pp. H1965-H1973 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink

We previously reported that mild deoxycorticosterone acetate (DOCA)-salt hypertension develops in the absence of generalized sympathoexcitation. However, sympathetic nervous system activity (SNA) is regionally heterogeneous, so we began to investigate the role of sympathetic nerves to specific regions. Our first study on that possibility revealed no contribution of renal nerves to hypertension development. The splanchnic sympathetic nerves are implicated in blood pressure (BP) regulation because splanchnic denervation effectively lowers BP in human hypertension. Here we tested the hypothesis that splanchnic SNA contributes to the development of mild DOCA-salt hypertension. Splanchnic denervation was achieved by celiac ganglionectomy (CGX) in one group of rats while another group underwent sham surgery (SHAM-GX). After DOCA treatment (50 mg/kg) in rats with both kidneys intact, CGX rats exhibited a significantly attenuated increase in BP compared with SHAM-GX rats (15.6 ± 2.2 vs. 25.6 ± 2.2 mmHg, day 28 after DOCA treatment). In other rats, whole body norepinephrine (NE) spillover, measured to determine if CGX attenuated hypertension development by reducing global SNA, was not found to be different between SHAM-GX and CGX rats. In a third group, nonhepatic splanchnic NE spillover was measured as an index of splanchnic SNA, but this was not different between SHAM (non-DOCA-treated) and DOCA rats during hypertension development. In a final group, CGX effectively abolished nonhepatic splanchnic NE spillover. These data suggest that an intact splanchnic innervation is necessary for mild DOCA-salt hypertension development but not increased splanchnic SNA or NE release. Increased splanchnic vascular reactivity to NE during DOCA-salt treatment is one possible explanation.


1993 ◽  
Vol 264 (4) ◽  
pp. F629-F636 ◽  
Author(s):  
N. Parekh ◽  
A. P. Zou ◽  
I. Jungling ◽  
K. Endlich ◽  
J. Sadowski ◽  
...  

A calibration technique was developed to quantify blood flow changes in the renal cortex and outer medulla in rats using platinum needle electrodes sensing partial pressure of locally generated hydrogen. Measurements were made in male and female rats to investigate sex differences in the humoral control and autoregulation of regional renal circulations. In males, both cortical and outer medullary blood flows were efficiently auto-regulated above an arterial pressure of 100 mmHg. The converting-enzyme inhibitor quinapril increased blood flow by 20% in both kidney zones, and inhibition of prostaglandin synthesis by indomethacin did not change the flow. In females, similar results were obtained only for the cortex; the medulla had a different response pattern. The blood flow was not autoregulated in the experimental pressure range up to 120 mmHg; quinapril did not change the flow, but indomethacin decreased the flow by 16% and at the same time restored its autoregulation capacity. We conclude that: 1) the medulla of female rats has a high basal level of vasodilator prostaglandins, which interferes with blood flow autoregulation in this kidney area, and 2) medullary flow in female rats is little affected by endogenous angiotensin.


2021 ◽  
Author(s):  
Robin M Forbes-Lorman

Abstract Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.


2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


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