scholarly journals Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation

2020 ◽  
Vol 11 ◽  
Author(s):  
Asim B. Dey ◽  
Sherif Khedr ◽  
James Bean ◽  
Leah L. Porras ◽  
Tamika D. Meredith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive ◽  
Peripheral Vasodilation

Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
M. David Percival ◽  
Sylvie Toulmond ◽  
Nathalie Coulombe ◽  
Wanda Cromlish ◽  
Sylvie Desmarais ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Cathepsin B ◽  
Plasma Renin ◽  
Renin Activity ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Arterial Blood ◽  
Gene Compensation

Abstract Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conclude that cathepsin B does not play a significant role in this process in rodents.

MO094SALT INFLUENCES UROMODULIN EXCRETION INDEPENDENT OF BLOOD PRESSURE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sheon Mary ◽  
Philipp Boder ◽  
Giacomo Rossitto ◽  
Lesley Graham ◽  
Kayley Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endoplasmic Reticulum ◽  
Direct Effect ◽  
Ex Vivo ◽  
Mrna Levels ◽  
Salt Loading ◽  
Spontaneously Hypertensive ◽  
Risk Variants ◽  
Wistar Kyoto

Abstract Background and Aims Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending epithelial (TAL) cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. Studies on UMOD overexpressing transgenic mice have shown that UMOD increases the tubular salt reabsorption via enhanced NKCC2 activity. We aimed to dissect the effect of salt-loading and blood pressure on the excretion of UMOD. Method Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats (n=8/sex/strain) were maintained on 1% NaCl for three weeks. Salt-loaded SHRSP were treated with nifedipine. Tubule isolation and ex vivo incubation with nifedipine were used to assess its direct effect on TAL. Results Urinary UMOD excretion was significantly reduced after salt loading in both strains (figure). In salt-loaded SHRSP, nifedipine treatment reduced blood pressure and urinary UMOD excretion. The reductions in urinary UMOD excretion were dissociated from unchanged kidney UMOD protein and mRNA levels, however, were associated with UMOD endoplasmic reticulum accumulation, thus suggesting secretion as a key regulatory step. Ex vivo experiments with TAL tubules showed that nifedipine did not have a direct effect on UMOD secretion. Conclusion Our data suggest a direct effect of salt on UMOD secretion independent of blood pressure and a potential role of endoplasmic reticulum stress on the control of UMOD secretion. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.

Role of endothelin in mediating postmenopausal hypertension in a rat model

2005 ◽  
Vol 288 (1) ◽  
pp. R229-R233 ◽  
Author(s):  
Licy L. Yanes ◽  
Damian G. Romero ◽  
Valeria E. Cucchiarelli ◽  
Lourdes A. Fortepiani ◽  
Celso E. Gomez-Sanchez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Spontaneously Hypertensive Rats ◽  
Renal Cortex ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Peptide Expression ◽  
Premenopausal Female

Cardiovascular disease is the leading cause of death in women after menopause. Hypertension, a major cardiovascular risk factor, becomes more prevalent after menopause. The mechanisms responsible for the increase in blood pressure (BP) in postmenopausal women are unknown. We have recently characterized the aged, postestrous-cycling (PMR) spontaneously hypertensive rats (SHR) as a model of postmenopausal hypertension. The purpose of the present study was to determine whether endothelin plays a role in the increased BP in PMR. Premenopausal female SHR, aged 4–5 mo (YF), and PMR, aged 16 mo, were studied. Expression of preproendothelin-1 mRNA was not different in either renal cortex or medulla between PMR and YF ( n = 7–8/group). In contrast, ET-1 peptide expression was significantly higher in renal cortex of PMR than in renal cortex of YF, but there was no difference in medullary ET-1. Expression of endothelin ETA receptor (ETAR) mRNA was lower in renal cortex and medulla of PMR than of YF. Additional groups of rats ( n = 6–7/group) were treated for 3 wk with the ETAR antagonist ABT-627 (5 mg·kg−1·day−1). BP was significantly higher in PMR than in YF. ETAR antagonist reduced BP in PMR by 20% to the level found in control YF. ETAR antagonist had no effect on BP in YF. These data support the hypothesis that the increase in BP in PMR is mediated in part by endothelin and the ETAR.

scholarly journals Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats.

2021 ◽  
Author(s):  
Sheon Mary ◽  
Philipp Boder ◽  
Giacomo Rossitto ◽  
Lesley Graham ◽  
Kayley Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Ex Vivo ◽  
Chronic Hypertension ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Salt Loading ◽  
Spontaneously Hypertensive

Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension. Normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) (n=8/sex/strain) were maintained on 1% NaCl for three weeks. A subset of salt-loaded SHRSP was treated with nifedipine. Salt-loading in SHRSP increased blood pressure (ΔSBP 35 ± 5 mmHg, p<0.0001) and kidney injury markers such as KIM-1 (fold change, FC 3.4; p=0.003), NGAL (FC, 2.0; p=0.012) and proteinuria. After salt-loading there was a reduction in urinary UMOD excretion in WKY and SHRSP by 26% and 55% respectively, compared to baseline. Nifedipine treatment reduced blood pressure in SHRSP, however, did not prevent salt-induced reduction in urinary UMOD excretion. In all experiments, changes in urinary UMOD excretion were dissociated from kidney UMOD protein and mRNA levels. Colocalization and ex-vivo studies showed that salt-loading increased intracellular UMOD retention in both WKY and SHRSP. Our study provides novel insights into the interplay between salt, UMOD, and blood pressure. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.

Abstract 352: Evaluation of Structural, Mechanical and Functional Properties in Small Arteries of Spontaneously Hypertensive Rats Before and After the Development of High Blood Pressure.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rafael M Jeuken ◽  
Luciana V Rossoni
Keyword(s):  
Blood Pressure ◽  
Mesenteric Arteries ◽  
Intraluminal Pressure ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wall Stiffness ◽  
Before And After ◽  
Wistar Kyoto ◽  
Picrosirius Red

Structural, mechanical and functional adjustments occur in small mesenteric arteries (SMA) of hypertensive models. However, the role of these properties to trigger hypertension is unknown. As expected, the systolic blood pressure was higher in adult (A, 6-month old) male SHR as compared to Wistar-Kyoto rats (WKY) (WKYA: 125±1.1 vs SHRA: 187±3.3 mmHg*); however, it was similar in young (Y, 6-week old) SHR as compared to age-matched WKY (WKYY: 117±1.8 vs SHRY: 120±2.1 mmHg). The 3rd order mesenteric arteries were mounted in a pressure myograph to analyze the structural [lumen diameter (L), cross sectional area (CSA), wall/lumen ratio (W/L)] and mechanical properties [β, representing wall stiffness]. Endothelium-dependent relaxation to acetylcholine (ACh, 10-10-10-5 M) or -independent relaxation to sodium nitroprusside (SNP, 10-9-10-4 M) were evaluated in SMA using wire myography. At the passive condition (Ca2+-free solution) and intraluminal pressure of 160 mmHg, the L was lower in SMA of both SHR (WKYY: 294±12.0 vs SHRY: 241±4.3*; WKYA: 353±4.7 vs SHRA: 283±6.2 μm*); while the W/L ratio was higher in SHR as compared to age-matched WKY. CSA was similar between age-matched groups. β value was higher in SHR independently of age (WKYY: 5.8±0.4 vs. SHRY: 7.8±0.4*; WKYA: 4.7±0.1 vs SHRA: 6.7±0.4*). The collagen area evaluated by picrosirius red staining was higher in SMA of SHRA as compared to WKYA (WKYA: 15±2.4 vs SHRA: 26±1.8%*), but it did not change in young rats. ACh-induced maximal relaxation was similar in SMA from young groups (WKYY: 93±3.8 vs SHRY: 92±3.1%); however, in SHRA ACh elicited a biphasic curve inducing contraction at concentrations higher than 10-7M, which was not observed in WKYA. Relaxation to SNP did not change among groups. Reactive oxygen species analyzed by dihydroethidium was higher in SMA of SHRA as compared to WKYA (WKYA: 100±3.7 vs SHRA: 126±10.3% of integrated density*), but did not change in young SMA. Although SMA of SHRY present eutrophic inward remodeling and wall stiffening, it does not present collagen deposition, oxidative stress or endothelial dysfunction as observed in SHRA; suggesting that vascular remodeling and wall stiffness of SMA are not sufficient to trigger hypertension, at least when endothelial function is preserved.

scholarly journals Electroacupuncture Improves Blood Pressure in SHRs by Regulating the Immune Balance between Th17 and Treg

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yang Wang ◽  
Lili Zhang ◽  
Li Li ◽  
Hantong Hu ◽  
Pan Pan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Th17 Cells ◽  
Spontaneously Hypertensive Rats ◽  
Treg Cells ◽  
T Helper ◽  
Hypertensive Rats ◽  
T Helper 17 ◽  
Spontaneously Hypertensive ◽  
Immune Balance

The present study investigated the effects of electroacupuncture on blood pressure in spontaneously hypertensive rats (SHRs) by regulating the immune balance of T helper 17 cells (Th17 cells) and regulatory T cells (Treg cells). This study investigated the role of electroacupuncture in the immune balance of SHRs using Western blot, flow cytometry, and ELISA techniques. Electroacupuncture significantly improved blood pressure, downregulated the expression of RORγt, and upregulated the expression of Foxp3, reduced the production of Th17 cells, promoted the production of Treg cells, reduced the secretion of IL-6 and IL-17, and increased the secretion of TGF-β1 and IL-10. These findings suggest that electroacupuncture therapy effectively improved the systolic blood pressure of SHRs, and its mechanism may be related to promotion of the immune balance between Th17 and Treg.

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