Abstract MP08: Testosterone Contributes To Renal Necrosis In Male Spontaneously Hypertensive Rats (SHR).

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Mahmoud Abdelbary ◽  
Ellen E Gillis ◽  
Jennifer C Sullivan
Keyword(s):  
Blood Pressure ◽  
Flow Cytometric Analysis ◽  
Tubular Epithelial Cell ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Flow Cytometric ◽  
Age Related ◽  
Renal Tubular ◽  
Renal Necrosis

We previously published a sex difference in renal necrosis in SHR with males having a maturation induced increase in renal necrosis that is absent in females. Testosterone is known to drive an increase both in blood pressure (BP) with maturation in male SHR and necrosis of renal tubular epithelial cell in vitro. In the current study we tested the hypothesis that testosterone underlies the maturation induced increase in renal necrosis in male SHR. At 4 weeks of age, male SHR were randomly assigned to either sham or gonadectomy (ORX) groups (n=3). To control for the influence of high BP on renal necrosis, a third group was subjected to a sham surgery and treated with the anti-hypertensive medications hydrochlorothiazide (HCTZ; 55mg/kg/day) and reserpine (Res; 4.5 mg/kg/day) in drinking water starting at 9 weeks of age (n=4) to prevent age-related increases in BP. At 8 weeks of age, telemeters were implanted in all groups followed by a recovery for 1 week before BP was recorded. A separate set of rats were randomly assigned to Sham (n=3), ORX (n=4), or HCTZ/Res (n=4) and subjected to the exact same procedures as the previous set except for telemetry implantation. All rats were euthanized at 13 weeks of age and kidneys were collected for the quantification of renal necrosis using flow cytometric analysis of 7AAD + cells. Data were analyzed using one-way ANOVA and presented as mean ± standard error. BP was significantly lower in ODX and HCTZ/Res treated groups compared to sham (mean arterial blood pressure (mmHg): Sham= 139±2; HCTZ/Res= 117±3; ODX= 126±2; p=0.002; n=3-4). Renal necrosis was also significantly less in ORX rats, but not altered in HCTZ/Res treated groups compared to sham (renal necrosis expressed as % total gated kidney cells: Sham= 6±0.3%; HCTZ/Res=5±0.4%; ODX= 4±0.4%; P=0.003; n=6-7). Testosterone contributes to maturation induced increase in renal necrosis in male SHR.

CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR

2001 ◽  
Vol 280 (1) ◽  
pp. R255-R261 ◽  
Author(s):  
Mong-Heng Wang ◽  
Fan Zhang ◽  
Jackleen Marji ◽  
Barbara A. Zand ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arachidonic Acid ◽  
Antisense Oligonucleotide ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Mesenteric Arteries ◽  
Arachidonic Acid Metabolite ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Renal Tubular

The cytochrome P-450 4A (CYP4A)-derived arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) affects renal tubular and vascular functions and has been implicated in the control of arterial pressure. We examined the effect of antisense oligonucleotide (ODN) to CYP4A1, the low K m arachidonic acid ω-hydroxylating isoform, on vascular 20-HETE synthesis, vascular reactivity, and blood pressure in the spontaneously hypertensive rat (SHR). Administration of CYP4A1 antisense ODN decreased mean arterial blood pressure from 137 ± 3 to 121 ± 4 mmHg ( P < 0.05) after 5 days of treatment, whereas treatment with scrambled antisense ODN had no effect. Treatment with CYP4A1 antisense ODN reduced the level of CYP4A-immunoreactive proteins along with 20-HETE synthesis in mesenteric arterial vessels. Mesenteric arteries from rats treated with antisense ODN exhibited decreased sensitivity to the constrictor action of phenylephrine (EC50 0.69 ± 0.17 vs. 1.77 ± 0.40 μM). Likewise, mesenteric arterioles from antisense ODN-treated rats revealed attenuation of myogenic constrictor responses to increases of transmural pressure. The decreased vascular reactivity and myogenic responses were reversible with the addition of 20-HETE. These data suggest that CYP4A1-derived 20-HETE facilitates myogenic constrictor responses in the mesenteric microcirculation and contributes to pressor mechanisms in SHR.

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

2002 ◽  
Vol 283 (3) ◽  
pp. R710-R720 ◽  
Author(s):  
Fengyun Xu ◽  
Wesley O. Straub ◽  
Winnie Pak ◽  
Ping Su ◽  
Kristopher G. Maier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Vasoconstrictor Response ◽  
Potent Vasoconstrictor ◽  
Acetylenic Fatty Acid ◽  
Regulation Of Blood Pressure

The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 ± 3.2 mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.

scholarly journals Splenectomy decreases blood pressure and abolishes sex differences in renal Tregs in spontaneously hypertensive rats

2021 ◽  
Author(s):  
Ellen E Gillis ◽  
Kasey Belanger ◽  
Mahmoud Abdelbary ◽  
Riyaz Mohamed ◽  
Jingping Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Sex Differences ◽  
Spontaneously Hypertensive Rats ◽  
Flow Cytometric Analysis ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Flow Cytometric

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHR) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared to males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 weeks and 14 weeks of age.  Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX, n=6) at 12 wks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHR, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

scholarly journals Antihypertensive effect of aqueous polyphenol extracts of Amaranthusviridis and Telfairiaoccidentalis leaves in spontaneously hypertensive rats

2018 ◽  
Vol 1 ◽  
Author(s):  
Olayinka A. Olarewaju ◽  
Adeola M. Alashi ◽  
Rotimi E Aluko
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Antihypertensive Agents ◽  
Hypertensive Rats ◽  
Leaf Extracts ◽  
Spontaneously Hypertensive ◽  
Angiotensin I Converting Enzyme ◽  
Arterial Blood ◽  
Renin Inhibition

The antihypertensive effects of aqueous polyphenol-rich extracts of Amaranthusviridis (AV) and Telfairiaoccidentalis (TO) leaves in spontaneously hypertensive rats (SHR) were investigated. The dried vegetable leaves were extracted using 1:20 (leaves:water, w/v) ratio for 4 h at 60 °C. Results showed significantly (P < 0.05) higher polyphenol contents in TO extracts (80–88 mg gallic acid equivalents, GAE/100 mg) when compared with the AV (62–67 mg GAE/100 mg). Caffeic acid, rutin and myricetin were the main polyphenols found in the extracts. The TO extracts had significantly (P < 0.05) higher in vitro inhibition of angiotensin I-converting enzyme (ACE) activity while AV extracts had better renin inhibition. Oral administration (100 mg/kg body weight) to SHR led to significant (P < 0.05) reductions in systolic blood pressure for the AV (−39 mmHg after 8 h)and TO (−24 mmHg after 4 and 8 h).The vegetable extracts also produced significant (P < 0.05) reductions in diastolic blood pressure, mean arterial blood pressure and heart rate when compared to the untreated rats. Thus both the AV and TO leaf extracts have the potential to be used as antihypertensive agents, especially the AV, which produced persistent long-lasting effect over a 24 h period.

Cardiovascular Effects of Micromeria graeca (L.) Benth. ex Rchb in Normotensive and Hypertensive Rats

2020 ◽  
Vol 20 (8) ◽  
pp. 1253-1261
Author(s):  
Mourad Akdad ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Arterial Blood Pressure ◽  
Antihypertensive Activity ◽  
Computer Assisted ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Arterial Blood

Aims: The present study was performed in order to analyze the antihypertensive activity of Micromeria graeca (L.) Benth. ex Rchb. Background: Micromeria graeca (L.) Benth. ex Rchb is an aromatic and medicinal plant belonging to the Lamiaceae family. This herb is used to treat various pathologies such as cardiovascular disorders. Meanwhile, its pharmacological effects on the cardiovascular system have not been studied. Objective: The present study aimed to evaluate the effect of aqueous extract of aerial parts of Micromeria graeca (AEMG) on the cardiovascular system in normotensive and hypertensive rats. Methods: In this study, the cardiovascular effect of AEMG was evaluated using in vivo and in vitro investigations. In order to assess the acute effect of AEMG on the cardiovascular system, anesthetized L-NAME-hypertensive and normotensive rats received AEMG (100 mg/kg) orally and arterial blood pressure parameters were monitored during six hours. In the sub-chronic study, rats were orally treated for one week, followed by blood pressure assessment during one week of treatment. Blood pressure was measured using a tail-cuff and a computer-assisted monitoring device. In the second experiment, isolated rat aortic ring pre-contracted with Epinephrine (EP) or KCl was used to assess the vasorelaxant effect of AEMG. Results: Oral administration of AEMG (100 mg/kg) provoked a decrease of arterial blood pressure parameters in hypertensive rats. In addition, AEMG induced a vasorelaxant effect in thoracic aortic rings pre-contracted with EP (10 μM) or KCl (80 mM). This effect was attenuated in the presence of propranolol and methylene blue. While in the presence of glibenclamide, L-NAME, nifedipine or Indomethacin, the vasorelaxant effect was not affected. Conclusion: This study showed that Micromeria graeca possesses a potent antihypertensive effect and relaxes the vascular smooth muscle through β-adrenergic and cGMP pathways.

Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An in vitro and in vivo Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Acute Experiment ◽  
Antihypertensive Activity ◽  
Mentha Pulegium ◽  
In Vitro Experiment ◽  
Arterial Blood ◽  
Dose Dependent ◽  
Ca2 Channels

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.

Effects of nicotine on canine intestinal blood flow and oxygen consumption

1984 ◽  
Vol 246 (2) ◽  
pp. G195-G203
Author(s):  
R. H. Gallavan ◽  
Y. Tsuchiya ◽  
E. D. Jacobson
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Muscle Tension ◽  
Intestinal Blood Flow ◽  
Mesenteric Blood Flow ◽  
State Response ◽  
Arterial Blood ◽  
Intestinal Circulation

The purpose of this study was to determine the effects of nicotine on intestinal blood flow and oxygen consumption. The intravenous infusion of nicotine at doses corresponding to those experienced by smokers produced a transient increase in systemic arterial blood pressure and mesenteric blood flow. Subsequently a steady-state response developed that consisted of a reduction in mesenteric blood flow due to both a decrease in blood pressure and an increase in intestinal vascular resistance. This increase in resistance was probably due to increased levels of circulating catecholamines. The intra-arterial infusion of nicotine into the intestinal circulation at doses experienced by the average smoker had no effect on either intestinal blood flow or oxygen consumption. Similarly, under in vitro conditions nicotine had no direct effect on intestinal vascular smooth muscle tension. Thus, nicotine appears to reduce intestinal blood flow indirectly as a result of its systemic effects.

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