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.

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.

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.

scholarly journals Effects of Prehypertensive Losartan Treatment on Resistance Vessel Remodeling and Angiotensin II Type 1 Receptor Expression in Spontaneously Hypertensive Rats

2020 ◽  
Vol 33 (5) ◽  
pp. 471-471
Author(s):  
Ting-jun Wang ◽  
Wan-ru Chen ◽  
Xu Lin ◽  
Gui-li Lian ◽  
Chang-sheng Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Resistance Vessel ◽  
Spontaneously Hypertensive ◽  
Vessel Remodeling ◽  
Wistar Kyoto ◽  
Losartan Treatment

Abstract Background To study the effects of prehypertensive losartan treatment on blood pressure, resistance vessel remodeling, and angiotensin II type 1 receptor (AT1R) expression in adult spontaneously hypertensive rats (SHRs). Methods Four-week-old SHR and Wistar-Kyoto rats were randomly divided into losartan-treated and untreated groups. Losartan was administrated by gavage from 4 to 10 weeks old. Blood pressure was monitored by the tail-cuff method till 26 weeks old. The third grade mesenteric arteries were then isolated. Vessel structure, relaxation reactivity, angiotensin II type 1 receptor expression, and angiotensin II levels were analyzed. Results Losartan treatment from 4 to 10 weeks of age significantly lowered systolic blood pressure from 10 to 26 weeks in SHR. At 26 weeks old, wall thickness to lumen radius and wall area to lumen area of mesenteric arteries were significantly lower in losartan-treated than untreated SHR (P < 0.01). Maximum relaxation to acetylcholine and its pD2 were increased in losartan-treated compared to untreated SHR (P < 0.01). Angiotensin II type 1 receptor mRNA and protein levels were significantly reduced in losartan-treated SHR (P < 0.01). However, angiotensin II levels in plasma and mesenteric arteries of losartan-treated SHR were higher than those of untreated SHR (P < 0.05). Losartan treatment lowered systolic blood pressure in Wistar-Kyoto at the age of 10 weeks (P < 0.05), but had no significant effect on blood pressure after 14 weeks or mesenteric arteries at 26 weeks. Conclusions Blood pressure reduction induced by prehypertensive losartan treatment ameliorates resistance vessel remodeling and downregulates angiotensin II type 1 receptor expression in adult SHR.

scholarly journals Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats

2010 ◽  
Vol 298 (6) ◽  
pp. H1769-H1775 ◽  
Author(s):  
YiLin Ren ◽  
Martin A. D'Ambrosio ◽  
Ruisheng Liu ◽  
Patrick J. Pagano ◽  
Jeffrey L. Garvin ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Perfusion Pressure ◽  
Intraluminal Pressure ◽  
Myogenic Response ◽  
Afferent Arteriole ◽  
Hypertensive Rats ◽  
Luminal Diameter ◽  
Spontaneously Hypertensive ◽  
Before And After ◽  
Wistar Kyoto

Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide (O2−) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 ± 2.9% in WKY Af-Arts but fell by 29.3 ± 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af-Arts compared with WKY Af-Arts (SHR, 48.0 ± 2.2%; and WKY, 12.2 ± 0.3%). To test whether O2− contributes to the myogenic response in SHRs, either the membrane-permeant O2− scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91 ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol (10−4 M) and gp91 ds-tat (10−5 M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure-induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived O2− may contribute to the enhanced myogenic response, and 3) O2− exerts little influence on the myogenic response under normotensive conditions.

scholarly journals Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
S. Bosnyak ◽  
R. E. Widdop ◽  
K. M. Denton ◽  
E. S. Jones
Keyword(s):  
Blood Pressure ◽  
Angiotensin Receptor ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Receptor Localization ◽  
Wistar Kyoto ◽  
Depressor Effect ◽  
Stimulation Of

Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT2R). However, the role of vascular AT2R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT1R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT2R antagonist, PD123319. In a separate group of animals, the specificMasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT2R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT2R blockade orMasR blockade. At the same time, AT2R,MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT2R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT2R andMasR.

Spontaneously hypertensive rat resistance artery structure related to myogenic and mechanical properties

2001 ◽  
Vol 101 (4) ◽  
pp. 385-393 ◽  
Author(s):  
Stuart J. BUND
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Wall Stress ◽  
Mesenteric Arteries ◽  
Maximum Pressure ◽  
Resistance Arteries ◽  
Contractile Responses ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wall Stiffness ◽  
Wistar Kyoto

This investigation related arterial structure to myogenic (pressure-dependent) contractile responses in resistance arteries from spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) normotensive control rats under pressurized conditions in vitro. Femoral and mesenteric resistance arteries from either strain were cannulated and pressurized in an arteriograph for the determination of pressure-diameter relationships under passive and active conditions in the range 5-200mmHg transmural pressure. Arterial geometrical measurements were made under relaxed conditions at 100mmHg. Media thickness/lumen diameter (M/L) ratios were significantly increased in SHR femoral (5.00±0.44% compared with 3.63±0.34%; P<0.05) and mesenteric (4.40±0.29% compared with 2.62±0.23%; P<0.001) arteries compared with those from WKY rats. Maximum myogenic contractions, assessed as minimum normalized diameters, were not significantly different in SHR and WKY rat femoral (0.41±0.03 and 0.40±0.02 respectively) or mesenteric (0.56±0.02 and 0.63±0.03 respectively) arteries. Arterial mechanical analyses demonstrated that incremental elastic modulus is reduced in SHR mesenteric arteries, but is not significantly different in SHR femoral arteries, compared with those from WKY rats. Additionally, wall stress at estimated in vivo pressures under passive and active conditions are similar in SHR and WKY rat arteries. These data demonstrate that increased M/L ratios in resistance arteries from SHRs are not associated with increased maximum pressure-dependent contractile responses. Increased M/L ratios in resistance arteries from SHRs are not accounted for by increased vessel wall stiffness, but the hypertension-associated arterial geometrical abnormalities act to normalize wall stress in the face of increased arterial pressure.

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats

1988 ◽  
Vol 74 (6) ◽  
pp. 577-585 ◽  
Author(s):  
F. C. Luft ◽  
H. Steinberg ◽  
U. Ganten ◽  
D. Meyer ◽  
K. H. Gless ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mineral Water ◽  
Sodium Reabsorption ◽  
Sodium Potassium ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Ph Values ◽  
Wistar Kyoto ◽  
Renal Sodium Reabsorption

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar–Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin–angiotensin–aldosterone system and 18-hydroxy-deoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower Pco2 and HCO−3 values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR

1996 ◽  
Vol 270 (6) ◽  
pp. R1265-R1272 ◽  
Author(s):  
E. Gaudet ◽  
J. Blanc ◽  
J. L. Elghozi
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Acute Administration ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Air Jet ◽  
Wistar Kyoto

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.

Central V1 AVP receptors are involved in cardiovascular adaptation to hypovolemia in WKY but not in SHR

1996 ◽  
Vol 271 (3) ◽  
pp. H1057-H1064 ◽  
Author(s):  
A. S. Budzikowski ◽  
P. Paczwa ◽  
E. Szczepanska-Sadowska
Keyword(s):  
Cardiovascular Responses ◽  
Receptor Antagonists ◽  
Question Mark ◽  
Spontaneously Hypertensive ◽  
Arterial Bleeding ◽  
Artificial Cerebrospinal Fluid ◽  
Before And After ◽  
Wistar Kyoto ◽  
Lateral Cerebral Ventricle

The present study was designed to determine the role of centrally released arginine vasopressin (AVP) in cardiovascular adaptation to hypotensive hypovolemia in conscious normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Three groups of experiments were performed on WKY and SHR chronically implanted with lateral cerebral ventricle (LCV) cannulas and with femoral artery catheters. Mean arterial pressure (MAP) and heart rate (HR) were monitored before and after arterial bleeding (1.3% body weight) performed during LCV infusion 1) artificial cerebrospinal fluid (control), 2) V1 AVP-receptor antagonists inverted question mark[d(Et2)Tyr(Me)]DAVP, 5 ng/min inverted question mark, and 3) V2 AVP-receptor antagonists inverted question mark[d(CH2)5-D-Ile2, Ile4, AlaNH2]AVP, 5 ng/min inverted question mark. In control experiments hemorrhage caused similar significant decreases of MAP in both strains and bradycardia in WKY. Blockade of central V1 AVP receptors abolished hemorrhagic bradycardia and significantly reduced hypotension in WKY, with no effect on HR and MAP responses to hypovolemia in SHR. Neither in WKY nor in SHR were the cardiovascular responses to hemorrhage altered by blockade of central V2 receptors. The results suggest that the central V1 AVP system plays a significant role in eliciting hypovolemic bradycardia and hypotension in WKY and that this function is significantly impaired in SHR.

Effects of endothelin 3 on diastolic blood pressure of pithed Sprague–Dawley, Wistar–Kyoto, and spontaneously hypertensive rats before and after pretreatment with nifedipine

1991 ◽  
Vol 69 (4) ◽  
pp. 531-535 ◽  
Author(s):  
Reza Tabrizchi ◽  
Christopher R. Triggle
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Diastolic Blood Pressure ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Pithed Rats ◽  
Before And After ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Endothelin 3

Pressor actions of endothelin 3 (ET3) were examined in pithed Sprague–Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive (SH) rats before and after the administration of the calcium channel antagonist, nifedipine. Systolic and diastolic blood pressures were recorded via an intra-arterial catheter from sodium pentobarbital anaesthized rats prior to pithing. The systolic and diastolic blood pressures recorded from SH rats were significantly greater than those of SD and WKY rats; however, after pithing there were no significant differences between the diastolic blood pressures among the various strains. Administration of nifedipine significantly reduced the diastolic blood pressure of pithed rats to an equal extent in all three strains. The infusion of ET3 produced a dose-dependent increase in diastolic blood pressure of SD, WKY, and SH rats, but neither vascular sensitivity nor reactivity to ET3 was altered in SH rats. Nifedipine was more effective at inhibiting the vasoactive actions of ET3 in SD and WKY than in SH rats. It was therefore concluded that the pressor actions of ET3 in SH rats may be less dependent on the influx of calcium through a dihydropyridine-sensitive calcium channel as compared with WKY and SD rats.Key words: endothelin 3, calcium antagonist, diastolic blood pressure, spontaneously hypertensive, pithed rats.

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