Vascular reactivity, tissue levels, and binding sites for endothelin: a comparison in the spontaneously hypertensive and Wistar–Kyoto rats

1991 ◽  
Vol 69 (3) ◽  
pp. 406-413 ◽  
Author(s):  
Gordon T. Bolger ◽  
Francine Liard ◽  
Annette Jodoin ◽  
Jorge Jaramillo
Keyword(s):  
Blood Pressure ◽  
Binding Sites ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Peripheral Resistance ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Arterial Blood ◽  
Wistar Kyoto

The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar–Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 ± 7 to 189 ± 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.Key words: endothelin, hypertension, spontaneously hypertensive rat.

Hyperresponsivitiy of spontaneously hypertensive rat to indirect measurement of blood pressure

1978 ◽  
Vol 234 (6) ◽  
pp. H690-H695 ◽  
Author(s):  
C. C. Chiueh ◽  
I. J. Kopin
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Catecholamines ◽  
Indirect Measurement ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Arterial Blood ◽  
Chromatographic Procedure ◽  
Wistar Kyoto

A chronic, indwelling, tail arterial cannula was implated in conscious undisturbed rats for measurement of blood pressure and heart rate and for obtaining blood samples. As an index of sympathetic activity, plasma levels of catecholamines in arterial blood of conscious animals were assayed by a radioenzymatic, paper-chromatographic procedure. Blood pressures of unrestrained spontaneously hypertensive (SHR) rats in their home cages (161 +/- 3/141 +/- 4 mmHg) were not different from those of pentobarbitol-anesthetized, hypertensive animals but were about 25 mmHg lower than awake animals during the restraint required for the tail-cuff procedure. Basal levels of plasma catecholamines in awake, undisturbed or in pentobarbital-anesthetized animals were similar in age-matched SHR and normotensive Wistar-Kyoto (WKY) rats. SHR rats were shown to have greater increase in plasma catecholamines than WKY rats during forced immobilization or restraint for indirect measurement of blood pressure.

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

1985 ◽  
Vol 63 (10) ◽  
pp. 1258-1262 ◽  
Author(s):  
Corey B. Toal ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Response ◽  
Receptor Occupancy ◽  
Pressure Response ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Freely Moving ◽  
Wistar Kyoto

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p < 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact consious SHR at 16 weeks of age.

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.

scholarly journals Effect of a methionine-supplemented diet on the blood pressure of Wistar–Kyoto and spontaneously hypertensive rats

2003 ◽  
Vol 89 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Sophie Robin ◽  
Véronique Maupoil ◽  
Frédérique Groubatch ◽  
Pascal Laurant ◽  
Alain Jacqueson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Homocysteine ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Complex Interactions ◽  
Methionine Concentration ◽  
Wistar Kyoto

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0·01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.

scholarly journals ACE Inhibition Reduces Infarction in Normotensive but Not Hypertensive Rats: Correlation with Cortical ACE Activity

2010 ◽  
Vol 30 (8) ◽  
pp. 1520-1526 ◽  
Author(s):  
Michelle J Porritt ◽  
Michelle Chen ◽  
Sarah SJ Rewell ◽  
Rachael G Dean ◽  
Louise M Burrell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Infarct Volume ◽  
Ace Inhibition ◽  
Artery Occlusion ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Wky Rats ◽  
Ace Activity ◽  
Wistar Kyoto

Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR.

scholarly journals Effects of hypertension on maternal adaptations to pregnancy: experimental study on spontaneously hypertensive rats

2001 ◽  
Vol 119 (2) ◽  
pp. 54-58 ◽  
Author(s):  
José Carlos Peraçoli ◽  
Marilza Vieira Cunha Rudge ◽  
Maria Salete Sartori ◽  
Roberto Jorge da Silva Franco
Keyword(s):  
Blood Pressure ◽  
Weight Gain ◽  
Spontaneously Hypertensive Rats ◽  
Sodium Retention ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Tail Cuff

CONTEXT: Animal models for essential hypertension have been used for understanding the human pathological conditions observed in pregnant hypertensive women. OBJECTIVE: To study the possible effects of pregnancy on hypertension and of hypertension on pregnancy in spontaneously hypertensive rats (SHR), and in their normotensive Wistar-Kyoto (WKY) counterparts. TYPE OF STUDY: Comparative study using laboratory animals. SETTING: Animal Research Laboratory of Clinical Medicine at the Medical School of Botucatu, São Paulo State University, Brazil. SAMPLE: Ten to twelve-week-old virgin female normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The animals were separated into four groups: 15 pregnant spontaneously hypertensive rats (SHR-P), 10 non-pregnant spontaneously hypertensive rats (SHR-NP), 15 pregnant normotensive rats (WKY-P), and 10 non-pregnant normotensive rats (WKY-NP). MAIN MEASUREMENTS: The blood pressure was evaluated by the tail cuff method, in rats either with or without prior training for the handling necessary for tail cuff measurements. The maternal volemia expansion was indirectly evaluated by weight gain, and by systemic parameters as hematocrit, hemoglobin, total protein, albumin and sodium retention. The perinatal outcome of pregnancy was evaluated by analysis of resorptions, litter size, rate of low weight and number of stillbirths. RESULTS: The late fall in blood pressure in the pregnant SHR strain and in the normotensive WKY strain can only be detected in rats previously trained to accept the handling necessary for the tail cuff measurement. During pregnancy the body weight gain was significantly higher in WKY than in SHR rats. Systemic parameters were significantly lower in pregnant WKY rats than in non-pregnant WKY rats, while no differences were observed between pregnant and non-pregnant SHR groups. In pregnant WKY rats the sodium retention was higher from the 13th day onwards, while in SHR rats this occurred only on the 21st day. The characteristics of reproductive function such as number and weight of fetus, perinatal mortality and the resorption rate were significantly affected in the SHR strain. CONCLUSION: The SHR strain may be considered as a model for chronic hypovolemic maternal hypertension, with the fetal growth retardation being determined by this hypovolemic state.

Altered aortic reactivity and lowered blood pressure associated with high calcium intake

1986 ◽  
Vol 251 (5) ◽  
pp. H976-H983 ◽  
Author(s):  
R. D. Bukoski ◽  
D. A. McCarron
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Isometric Force ◽  
Control Diet ◽  
Shr Rats ◽  
High Calcium Intake ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
High Calcium ◽  
Wistar Kyoto

The hypothesis that dietary calcium (dCa) alters functional properties of aortic smooth muscle in the spontaneously hypertensive rat (SHR) was tested. At 6 wk of age, Wistar Kyoto (WKY) and (SHR) rats were placed on a control diet containing 1% Ca. The experimental SHR group received a 2%-calcium diet. After an average of either 8 or 15 wk on the diets (WOD), aortic rings were prepared for measurement of passive elastic properties and isometric force development. Differences in blood pressure (BP) were not apparent until after 8 WOD when the BP of SHRs on 2% dCa were 10-15 mmHg lower than SHRs on 1% dCa (P less than 0.05). After 8 WOD, when the BP effect first emerged, no significant differences in aortic properties were observed between the SHR groups. However, after 15 WOD, aortas of SHRs on 2% dCa were more compliant than those of SHRs on 1% dCa and between 8 and 15 WOD the sensitivity to KCl decreased in aortas from the WKY group and the SHRs on 2% dCa, but not the SHR-1% dCa group (mean effective dose went from 14.4 +/- 0.4 to 18.5 +/- 0.9 mM for WKY and from 13.6 +/- 0.6 to 17.1 +/- 1.2 mM for SHRs on 2% dCa, P less than 0.05). In addition, between 8 and 15 WOD, a significant decrease in response to a calcium (Ca2+) challenge after removal of K+ and Ca2+ occurred in aortas of the SHRs on 2% dCa, but not in the control diet groups, indicating that a decrease in aortic reactivity was present in the Ca2+-supplemented SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Philip R. Griffiths ◽  
Stephen J. Lolait ◽  
Julian F. R. Paton ◽  
Anne-Marie O’Carroll
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Circumventricular Organs ◽  
Major Question ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Apelin Receptor ◽  
Wistar Kyoto

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr1]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr1]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr1]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr1]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR.

Time-Dependent Effects of Individual and Combined Treatments With Nebivolol, Lisinopril, and Valsartan on Blood Pressure and Vascular Reactivity to Angiotensin II and Norepinephrine

2021 ◽  
pp. 107424842110018
Author(s):  
Diego Lezama-Martinez ◽  
Maria Elena Hernandez-Campos ◽  
Jazmin Flores-Monroy ◽  
Ignacio Valencia-Hernandez ◽  
Luisa Martinez-Aguilar
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Reduce Blood Pressure ◽  
Time Dependent ◽  
Spontaneously Hypertensive ◽  
Sympathetic Nervous Systems ◽  
Wistar Kyoto ◽  
Concentration Response Curve

Clinical guidelines suggest the combination of 2 drugs as a strategy to treat hypertension. However, some antihypertensive combinations have been shown to be ineffective. Therefore, it is necessary to determine whether differences exist between the results of monotherapy and combination therapy by temporal monitoring of the responses to angiotensin II and norepinephrine, which are vasoconstrictors involved in the development of hypertension. Thus, the purpose of this work was to determine the vascular reactivity to angiotensin II and norepinephrine in spontaneously hypertensive rat (SHR) aortic rings after treatment with valsartan, lisinopril, nebivolol, nebivolol-lisinopril, and nebivolol-valsartan for different periods of time. In this study, male SHR and Wistar Kyoto normotensive (WKY) rats were divided into 7 groups treated for 1, 2, and 4 weeks: (1) WKY + vehicle, (2) SHR + vehicle; (3) SHR + nebivolol; (4) SHR + lisinopril; (5) SHR + valsartan; (6) SHR + nebivolol-lisinopril; and (7) SHR + nebivolol-valsartan. Blood pressure was measured by the tail-cuff method, and vascular reactivity was determined from the concentration-response curve to angiotensin II and norepinephrine in aortic rings. The results showed that the combined and individual treatments reduced mean blood pressure at all times evaluated. All treatments decreased vascular reactivity to angiotensin II; however, in the case of lisinopril and nebivolol-lisinopril, the effect observed was significant up to 2 weeks. All treatments decreased the reactivity to norepinephrine up to week 4. These results show a time-dependent difference in vascular reactivity between the pharmacological treatments, with nebivolol-valsartan and nebivolol-lisinopril being both effective combinations. Additionally, the results suggest crosstalk between the renin-angiotensin and sympathetic nervous systems to reduce blood pressure and to improve treatment efficacy.

The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat

1986 ◽  
Vol 64 (6) ◽  
pp. 748-750 ◽  
Author(s):  
Edward K. Y. Chiu ◽  
J. Robert McNeill
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Hypertensive Rats ◽  
Prolonged Infusion ◽  
Spontaneously Hypertensive ◽  
Control Value ◽  
Arterial Blood ◽  
Wistar Kyoto

In spontaneously hypertensive rats (SHR) and their normotensive Wistar–Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 μg∙kg−1∙min−1 for 3 h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 ± 3.3 to 146 ± 3.9 mmHg (p < 0.01), whereas pressure in WKY had fallen from 116 ± 3.0 to 107 ± 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p < 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.

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