Genetic basis for altered vascular responses to ouabain and potassium-free solution in hypertension

1986 ◽  
Vol 251 (6) ◽  
pp. H1276-H1282 ◽  
Author(s):  
C. A. Bruner ◽  
J. H. Myers ◽  
C. F. Sing ◽  
P. T. Jokelainen ◽  
R. C. Webb
Keyword(s):  
Blood Pressure ◽  
Genetic Basis ◽  
Genetic Factors ◽  
Isometric Force ◽  
Free Solution ◽  
Half Time ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
F2 Progeny

Many properties intrinsic to vascular smooth muscle are altered in hypertension. It is unknown whether these abnormalities are primary traits that may contribute to the etiology of hypertension or whether these vascular differences between the hypertensive and normotensive strains are inherited independently of genetic factors that predispose to hypertension. To determine if genetic factors responsible for the predisposition for hypertension may be the same as or linked to genetic factors determining a specific vascular response, adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and progeny of genetic crosses of SHRSP and WKY rats (F1, F2, F1 X WKY, F1 X SHRSP) were studied. Rats were killed and helical aortic strips were mounted in a tissue bath for isometric force recording. Contractile responses to 10(-3) M ouabain (expressed as a percent of force generated to a maximal depolarizing stimulus) were greater in aortas from SHRSP (90 +/- 9%) compared with aortas from WKY rats (38 +/- 5%, P less than 0.05). The half time for contraction in K+-free solution was more rapid in aortas from SHRSP (21 +/- 4 min) when compared with aortas from WKY rats (48 +/- 4 min, P less than 0.05). A significant positive correlation between blood pressure (tail-cuff method) and the contractile response to 10(-3) M ouabain was observed in the segregating F2 progeny. In contrast, no correlation between blood pressure and the half time for contraction in K+-free solution was observed in the segregating F2 progeny.(ABSTRACT TRUNCATED AT 250 WORDS)

Contractile responses to ouabain and K+-free solution in aorta from hypertensive rats

1986 ◽  
Vol 250 (4) ◽  
pp. H612-H619 ◽  
Author(s):  
R. S. Moreland ◽  
T. C. Major ◽  
R. C. Webb
Keyword(s):  
Channel Blocker ◽  
Isometric Force ◽  
Maximal Response ◽  
Na Channel ◽  
Free Solution ◽  
Contractile Responses ◽  
Spontaneously Hypertensive ◽  
Force Development ◽  
Monensin A ◽  
Wistar Kyoto

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Effects of Bromocriptine on Blood Pressure and Plasma β-Endorphin in Spontaneously Hypertensive Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 343s-345s ◽  
Author(s):  
J. S. Hutchinson ◽  
R. Di Nicolantonio ◽  
A. Lim ◽  
J. Clements ◽  
J. W. Funder
Keyword(s):  
Blood Pressure ◽  
Plasma Levels ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intravenous Injections ◽  
Wky Rats ◽  
Wistar Kyoto

1. Immunoreactive β-endorphin (IR-βEP) was two- to three-fold higher in pituitary neuro-intermediate lobes (N-IL) of spontaneously hypertensive rats (SHR) than of normotensive Wistar—Kyoto (NT-WKY) controls. 2. Plasma levels of IR-βEP were lower in SHR than in NT-WKY rats. 3. Intravenous injections of morphine lowered blood pressure of both SHR and NT-WKY rats to the same level; naloxone restored blood pressure of both groups to pre-morphine values. 4. Infusion of bromocriptine in SHR for 1 week lowered blood pressure and N-IL IR-βEP concentration. 5. These results confirm and extend postulated dopaminergic defect in this model of hypertension.

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.

Genetic predisposition to stroke in spontaneously hypertensive rats

1976 ◽  
Vol 230 (5) ◽  
pp. 1354-1359 ◽  
Author(s):  
A Nagaoka ◽  
H Iwatsuka ◽  
Z Suzuoki ◽  
K Okamoto
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Salt Solution ◽  
Spontaneously Hypertensive Rats ◽  
Genetic Factors ◽  
Experimental Period ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Average Blood Pressure ◽  
Wistar Kyoto

Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR.

Abstract 439: Role of Hindbrain Endogenous Melanocortin Receptor Activity in Contributing to Hypertension in SHR

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jussara M do Carmo ◽  
Alexandre A da SIlva ◽  
Zhen Wang ◽  
John E Hall
Keyword(s):  
Blood Pressure ◽  
Recovery Period ◽  
Elevated Blood Pressure ◽  
Metabolic Effects ◽  
Melanocortin Receptor ◽  
Elevated Blood ◽  
Melanocortin System ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto

We previously demonstrated that activation of the central nervous system (CNS) melanocortin system plays a key role in the modulation of sympathetic nerve activity (SNA) and blood pressure (BP) regulation. In the present study, we examined whether chronic inhibition of melanocortin-4 receptors (MC4R) in the hindbrain attenuates the elevated blood pressure in spontaneously hypertensive rats (SHR). The long-term cardiovascular and metabolic effects of MC4R antagonism were assessed in SHR and normotensive Wistar-Kyoto (WKY) rats. Male WKY rats (n=6) and SHR (n=7) were implanted with telemetry probes to measure BP and heart rate (HR) 24-hrs/day, and an intracerebroventricular (ICV) cannula was placed into the fourth ventricle (4 th V). After 10 days of recovery and 5 days of control measurements, the MC4R antagonist (SHU-9119, 1 nmol/h, 4 th V) was infused for 10 days followed by a 5-day recovery period. Chronic hindbrain MC4R antagonism significantly increased food intake and body weight in WKY (17±1 to 35±2 g/day and 280±8 to 353±8 g) and SHR (19±2 to 35±2 g/day and 323±7 to 371±11 g). No changes were observed in blood glucose levels (99±4 to 87±4 and 89±5 to 89±4 mg/dl, respectively for WKY and SHR). Chronic SHU-9119 infusion reduced MAP and HR similarly in WKY (-5±1 mmHg and -47±3 bpm) and SHR (-8±3 mmHg and -44±3 bpm). These results suggest that although hindbrain MC4R activity is important for appetite and HR regulation, it does not play a major role in mediating the elevated blood pressure in SHR. (NHLBI-PO1 HL51971/AHA SDG5680016)

Increases in CSF [Na+] precede the increases in blood pressure in Dahl S rats and SHR on a high-salt diet

2004 ◽  
Vol 287 (3) ◽  
pp. H1160-H1166 ◽  
Author(s):  
Bing S. Huang ◽  
Bruce N. Van Vliet ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
High Salt ◽  
Initial Increase ◽  
Primary Role ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Wistar Kyoto

In Dahl salt-sensitive (S) and salt-resistant (R) rats, and spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at 5–6 wk of age, a cannula was placed in the cisterna magna, and cerebrospinal fluid (CSF) was withdrawn continuously at 75 μl/12 h. CSF was collected as day- and nighttime samples from rats on a regular salt intake (0.6% Na+; R-Na) and then on a high salt intake (8% Na+; H-Na). In separate groups of rats, the abdominal aorta was cannulated and blood pressure (BP) and heart rate (HR) measured at 10 AM and 10 PM, with rats first on R-Na and then on H-Na. On H-Na, CSF [Na+] started to increase in the daytime of day 2 in Dahl S rats and of day 3 in SHR. BP and HR did not rise until day 3 in Dahl S rats and day 4 in SHR. In Dahl R and WKY rats, high salt did not change CSF [Na+], BP, or HR. In a third set of Dahl S rats, sampling of both CSF and BP was performed in each individual rat. Again, significant increases in CSF [Na+] were observed 1–2 days earlier than the increases in BP and HR. In a fourth set of Dahl S rats, BP and HR were recorded continuously by means of radiotelemetry for 5 days on R-Na and 8 days on H-Na. On H-Na, BP (but not HR) increased first in the nighttime of day 2. In another set of Dahl S rats, intracerebroventricular infusion of antibody Fab fragments binding ouabain-like compounds (OLC) with high affinity prevented the increase in BP and HR by H-Na but further increased CSF [Na+]. Finally, in Wistar rats on H-Na, intracerebroventricular infusion of ouabain increased BP and HR but decreased CSF [Na+]. Thus, in both Dahl S and SHR on H-Na, increases in CSF [Na+] preceded the increases in BP and HR, consistent with a primary role of increased CSF [Na+] in the salt-induced hypertension. An increase in brain OLC in response to the initial increase in CSF [Na+] appears to attenuate further increases in CSF [Na+] but at the “expense” of sympathoexcitation and hypertension.

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